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1.
Rev. chil. endocrinol. diabetes ; 15(2): 63-70, 2022. tab
Article in Spanish | LILACS | ID: biblio-1391657

ABSTRACT

La metformina es un hipoglicemiante ampliamente utilizado en el tratamiento de mujeres con síndrome de ovario poliquístico (SOP) por su acción como sensibilizante a la insulina, demostrando tener múltiples efectos favorables en parámetros clínicos y bioquímicos. Especial interés ha causado la variabilidad interindividual en el tratamiento con metformina, que se manifiesta con una respuesta subóptima en diversos grados o con la presencia de efectos adversos, principalmente gastrointestinales. Hasta ahora, pocos estudios han caracterizado este fenómeno en el SOP, así como los mecanismos que le subyacen. Se ha propuesto que variantes de genes envueltos en el transporte y acción de metformina podrían contribuir a la heterogeneidad de su respuesta. En este sentido, se han identificado polimorfismos de nucleótidos únicos (SNPs) en los transportadores de cationes orgánicos, en las proteínas de extrusión de múltiples fármacos y toxinas, y en proteínas quinasas; cuyas principales acciones son a nivel intestinal, hepático y renal, afectando la absorción, distribución y excreción de metformina, probablemente por modificaciones en su farmacocinética. Hasta ahora los escasos estudios disponibles en el SOP han identificado SNPs que estarían afectando la eficacia del tratamiento, sin embargo, no se ha profundizado en los efectos adversos asociados a las variantes genéticas. Es evidente que dichas variantes tienen relevancia clínica y que debieran ser consideradas al diseñar un tratamiento farmacológico, para optimizar su efectividad y minimizar reacciones adversas. El objetivo de este artículo es revisar la información sobre las variantes genéticas asociadas a la variabilidad en la respuesta del tratamiento con metformina en el SOP.


Metformin is a hypoglycemic agent widely used in the treatment of women with Polycystic Ovary Syndrome (PCOS) due to its action as an insulin sensitizer and its multiple favorable effects on clinical and biochemical parameters. There is great concern regarding the inter-individual variability in the response to metformin treatment, which may manifest as a suboptimal effect to varying degrees or by the presence of adverse effects, mainly gastrointestinal. Until now, scarce studies have characterized this phenomenon in PCOS, as well as the mechanisms that underlie it. It has been proposed that genetic variants involved in metformin transport and action could contribute to the heterogeneity of its response. In this sense, single nucleotide polymorphisms (SNPs) have been identified in organic cation transporters, in multidrug and toxin extrusion proteins, and in protein kinases; whose main actions are at the intestinal, hepatic and renal levels, affecting the absorption, distribution and excretion of metformin, probably due to modifications in the pharmacokinetics of the drug. Until now, the few studies available on PCOS have identified SNPs that may be affecting the efficacy of the treatment. However, the adverse effects associated with genetic variants have not been studied in depth. These variants may have clinical relevance and should be considered when designing a pharmacological treatment, to optimize its effectiveness and minimize adverse reactions. The objective of this article is to review the information on genetic variants associated with variability in the response to metformin treatment in PCOS.


Subject(s)
Humans , Female , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/drug therapy , Hypoglycemic Agents/adverse effects , Metformin/adverse effects , Genetic Variation , Polymorphism, Single Nucleotide
2.
Rev. Assoc. Med. Bras. (1992) ; 67(8): 1130-1136, Aug. 2021. tab
Article in English | LILACS | ID: biblio-1346987

ABSTRACT

SUMMARY OBJECTIVE The aim of this study was to investigate whether TCF7L2 gene mutation rs7903146 is in association with polycystic ovary syndrome (PCOS). METHODS A total of 44 PCOS and 48 control participants were recruited for this study. After DNA extraction from peripheral blood, quantitative PCR method was used for genotyping. With a case-control study design, two groups were compared for genotype and allele frequencies as well as clinical characteristics. RESULTS Mean testosterone level was significantly higher in PCOS group, whereas mean progesterone level was significantly higher in control group. In PCOS group, mean thyroid-stimulating hormone (TSH) level was significantly higher in polymorphic allele carriers. Genotype and allele frequencies were not different between groups. CONCLUSIONS When investigated for the first time in a population from Turkey, no association between PCOS and TCF7L2 gene rs7903146 polymorphism was detected. However, considering contradictory results of other populations and low cohort scale of this study, replication studies with greater cohorts are needed.


Subject(s)
Humans , Female , Diabetes Mellitus, Type 2 , Polycystic Ovary Syndrome/genetics , Turkey , Case-Control Studies , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Transcription Factor 7-Like 2 Protein/genetics , Gene Frequency , Genotype , Mutation
3.
Article in Chinese | WPRIM | ID: wpr-887935

ABSTRACT

This study used network pharmacology and molecular docking to study the mechanism of Bushen Culuan Formula in the treatment of infertility caused by polycystic ovary syndrome(PCOS). The active ingredients and potential drug targets of Bushen Cu-luan Decoction were obtained by searching the Traditional Chinese Medicine System Pharmacology(TCMSP) database, and the targets of PCOS by searching GeneCards. After the drug targets and disease targets were corrected by Uniprot, the intersection genes were obtained. STRING database and Cytoscape 3.7.2 were used for protein-protein interaction(PPI) analysis of the intersection genes. The ClueGO plug-in of Cytoscape 3.7.2 was employed to perform gene ontology(GO) enrichment and KEGG pathway enrichment for the intersection genes. Finally, molecular docking of the key active ingredients with the targets of Bushen Culuan Formula was performed using AutoDockVina and MGLtools. A total of 136 active ingredients and 314 drug targets of the decoction were obtained from TCMSP, and 136 disease targets from GeneCards. Finally, 49 drug-disease intersection genes were obtained. GO enrichment found that the genes were mainly involved in the regulation of muscle cell apoptosis, positive regulation of small molecule metabolism, core promoter binding, RNA polymerase Ⅱ regulation of pri-miRNA transcription, negative regulation of transmembrane transport and other biological functions. The enriched KEGG pathways mainly included MAPK, PI3 K-Akt, p53, and HIF-1 signaling pathways. The results of molecular docking showed that quercetin and PTGS2 can bind stably and interact through amino acid residues THR206, TRP387, ASN382, etc. This study preliminarily reveals the multi-component, multi-target, and multi-pathway mechanism of Bushen Culuan Formula in the treatment of PCOS-related infertility, which provides a basis for further research.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Female , Gene Ontology , Humans , Medicine, Chinese Traditional , Molecular Docking Simulation , Polycystic Ovary Syndrome/genetics , Signal Transduction
4.
Rev. Assoc. Med. Bras. (1992) ; 66(11): 1560-1565, Nov. 2020. tab, graf
Article in English | LILACS, SES-SP | ID: biblio-1143635

ABSTRACT

SUMMARY BACKGROUND: This study aimed to investigate the deletion polymorphisms of the genes of the glutathione S-transferase family GSTT1 and GSTM1 in patients with Polycystic Ovarian Syndrome (PCOS), comparing them with a control population. METHODS: Blood was collected from 219 women (110 with PCOS and 109 controls) and genomic DNA was extracted. For the analysis of polymorphisms, the technique used was multiplex PCR. In the statistical analysis, the chi-square test and multiple logistic regression were used. RESULTS: There is no association between the GSTM1 null and GSTT1 null genotypes with PCOS when analyzed separately (P = 0.616 and P = 0.188). The analysis of the combined genotypes showed differences between the groups (P < 0.05), evidencing that the genotypic combination GSTT1 positive and GSTM1 negative is more frequent among patients. In the multivariate analysis, smoking was more frequent in the control group (OR = 0.22; 95% CI - 0.87-0.57; P = 0.002) while the presence of a family history of PCOS (OR = 2, 96; 95% CI - 1.54-5.68; P = 0.001) was more frequent in women with PCOS. CONCLUSIONS: In the studied sample, the deletion polymorphisms of the GSTT1 and GSTM1 genes isolated are not associated with PCOS, but in combination, they may be implicated in the etiology of the condition.


RESUMO OBJETIVO: Este estudo teve como objetivo investigar os polimorfismos de deleção dos genes da família glutationa S-transferase GSTT1 e GSTM1 em pacientes com síndrome dos ovários policísticos (SOP), comparando-as com uma população controle. MÉTODOS: Foi colhido sangue de 219 mulheres (110 com SOP e 109 controles) e extraído o DNA genômico. Para análise dos polimorfismos, a técnica empregada foi PCR multiplex. Na análise estatística foi utilizado o teste do qui-quadrado e regressão logística múltipla. RESULTADOS: Não há associação dos genótipos GSTM1 nulo e GSTT1 nulo com SOP quando analisados isoladamente (p=0,616 e p=0,188). A análise dos genótipos combinados mostrou diferenças entre os grupos (p<0,05), evidenciando que a combinação genotípica GSTT1 positivo e GSTM1 negativo é mais frequente entre as pacientes. Na análise multivariada, o hábito tabagista foi mais frequente no grupo controle (OR=0,22; IC 95% - 0,87-0,57; p=0,002), enquanto que a presença do histórico de SOP familiar (OR=2,96; IC 95% - 1,54-5,68; p=0,001) foi mais frequente nas mulheres com SOP. CONCLUSÕES: Na casuística estudada, os polimorfismos de deleção dos genes GSTT1 e GSTM1 isolados não estão associados a SOP, mas em combinação podem estar implicados na etiologia da condição.


Subject(s)
Humans , Female , Polycystic Ovary Syndrome/genetics , Glutathione Transferase/genetics , Case-Control Studies , Risk Factors , Genetic Predisposition to Disease , Genotype
5.
Rev. Assoc. Med. Bras. (1992) ; 66(10): 1396-1401, Oct. 2020. tab, graf
Article in English | LILACS, SES-SP | ID: biblio-1136166

ABSTRACT

SUMMARY OBJECTIVE: The relationship between the clinicopathological and sociodemographics characteristics of acral melanomas diagnosed at BACKGROUND: This study aimed to investigate the frequency of VEGF gene insertion (I) / deletion (D) polymorphism (rs35569394) in patients with Polycystic Ovarian Syndrome (PCOS) and to compare with a control population to verify its association with the pathology. METHODS: 206 women participated in this study, 103 with PCOS (group of patients) and 103 without the disease (control group). After extraction of genomic DNA from the samples, molecular analysis was performed by Polymerase Chain Reaction (PCR) and electrophoresis in polycrylamide. Descriptive analysis, univariate analysis and logistic regression model were used. Results were presented in odds ratio (OR) and 95% confidence interval (95% CI), considering the significance of p <0.05. RESULTS: There were no statistical differences between patients and controls for allele frequencies (χ2 = 1.16, p = 0.56). The genotypic frequency distribution was in Hardy Weinberg equilibrium for the patients (χ2 = 2.42; p <0.05), but not for the control group (χ2 = 7.26; p <0.05). Regarding risk factors for the syndrome, a history of familial PCOS is more frequent among women with the syndrome. CONCLUSIONS: In the present study, there is no association between VEGF gene I / D polymorphism and PCOS.


RESUMO OBJETIVO: Este estudo teve como objetivo investigar a frequência do polimorfismo de inserção (I)/ deleção (D) do gene VEGF (rs35569394) em pacientes com Síndrome dos Ovários Policísticos (SOP) e comparar com uma população controle para verificar sua associação com a patologia. MÉTODOS: Participaram desse estudo 206 mulheres sendo 103 com SOP (grupo de pacientes) e 103 sem a doença (grupo controle). Após extração do DNA genômico das amostras, a análise molecular foi realizada por Reação em Cadeia da Polimerase e eletroforese em gel de poliacrilamida. Utilizou-se análise descritiva, análise univariada e modelo de regressão logística. Os resultados foram apresentados em odds ratio (OR) e intervalo de confiança de 95% (IC-95%), considerando a significância de p < 0,05. RESULTADOS: Não houve diferenças estatísticas entre as pacientes e controles para as frequências alélicas (χ2 = 1,16, p = 0,56). A distribuição da frequência genotípica estava em equilíbrio de Hardy Weinberg para as pacientes (χ2= 2,42; p<0,12), mas não para o grupo controle (χ2= 7,26; p<0,05). Em relação aos fatores de risco para a síndrome, a história de SOP familiar é mais frequente entre as mulheres com a síndrome. CONCLUSÕES: Na casuística estudada, não há associação entre o polimorfismo I/D do gene da VEGF e a SOP.


Subject(s)
Humans , Female , Polycystic Ovary Syndrome/genetics , Vascular Endothelial Growth Factor A/genetics , Case-Control Studies , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Alleles , Gene Frequency , Genotype
6.
Arch. endocrinol. metab. (Online) ; 64(1): 11-16, Jan.-Feb. 2020. tab
Article in English | LILACS | ID: biblio-1088769

ABSTRACT

ABSTRACT Objective The aim of this study was to assess the serum vitamin D level in a retrospective study in women with polycystic ovary syndrome (PCOS), according to the different phenotypes of the disease. Subjects and methods In this retrospective study, the records of 351 infertile women who were diagnosed with PCOS were examined, and 200 of them were enrolled in the study randomly in 4 PCOS phenotypes. Fifty normal ovulatory women with the history of male factor were selected as the control group. Parameters, including age, infertility duration, body mass index (BMI), hormone profile, as well as the serum vitamin D level were compared among the 4 phenotypes, with the P-value ≤ 0.05 considered statistically significant. Results The findings showed a higher serum vitamin D level in the control group than in PCOS patients, which was statistically significant (P < 0.001). In addition, there was no significant difference in the serum vitamin D level among the four phenotypes of PCOS. Conclusions No significant difference was found in the serum vitamin D level of the different phenotypes of PCOS. Further studies with larger sample sizes are recommended to be done to establish the role of the serum vitamin D level in PCOS patients.


Subject(s)
Humans , Female , Adolescent , Adult , Young Adult , Polycystic Ovary Syndrome/blood , Vitamin D/blood , Infertility, Female/blood , Phenotype , Polycystic Ovary Syndrome/genetics , Body Mass Index , Case-Control Studies , Retrospective Studies
7.
Chinese Acupuncture & Moxibustion ; (12): 1154-1158, 2020.
Article in Chinese | WPRIM | ID: wpr-877578

ABSTRACT

OBJECTIVE@#To compare the clinical effect of the combined treatment of acupuncture, moxibustion, Chinese herbal medicine and western medication and simple western medication on polycystic ovary syndrome (PCOS) of kidney deficiency and blood stagnation pattern and explore the effect on endometrial receptivity and the expression of serum homeobox gene A10 (HOXA10).@*METHODS@#A total of 60 patients with PCOS of kidney deficiency and blood stagnation pattern were randomized into a combined treatment group and a western medication group, 30 cases in each one. In the western medication group, on the fifth day of menstruation, clomiphene citrate tablets were taken orally, 50 mg each time, once daily, consecutively for 5 days. On the day when the follicle diameter was ≥ 18 mm, chorionic gonadotrophin for muscular injection, a dose of 10 000 U was given. Before sleep, the aspirin enteric-coated tablets were taken orally, 50 mg (except during menstruation). In the combined treatment group, on the base of the treatment as the western medication group, acupuncture and moxibustion were adopted and the Chinese herbal for tonifying the kidney and activating blood circulation was taken orally. The acupoints were Guanyuan (CV 4), Qihai (CV 6), Zusanli (ST 36), Sanyinjiao (SP 6), Zigong (EX-CA 1), etc. Acupuncture was remained for 30 min each time, once every two days and discontinued during menstruation. Chinese herbal was given from the 3rd day of menstruation till the onset of the next menstruation, one dose each day. After consecutive treatment for 3 menstrual cycles in the two groups, the real-time polymerase chain reaction (RT-PCR) method was adopted to determine the expression of serum HOXA10 before and after treatment in the patients of the two groups. The endometrial thickness at ovulatory phase, uterine arterial flow 7 days after ovulation [including uterine arterial pulsatility index (PI), resistance index (RI), peak systolic velocity (PSV)/end diastolic velocity (EDV), meaning S/D], pregnancy rate and the score of Chinese medicine symptoms before and after treatment were compared in the patients between the two groups.@*RESULTS@#① After treatment, the expression of serum HOXA10 was higher than that before treatment in the patients of the two groups (@*CONCLUSION@#The combined treatment with acupuncture, moxibustion and medication effectively improves endometrial receptivity and uterine arterial flow in the patients with PCOS of kidney deficiency and blood stagnation pattern and increases pregnancy rate. The therapeutic effect is better than the simple western medication and its mechanism is probably related to the regulation of serum HOXA10 expression.


Subject(s)
Acupuncture Points , Acupuncture Therapy , Female , Genes, Homeobox , Homeobox A10 Proteins , Humans , Kidney , Moxibustion , Polycystic Ovary Syndrome/genetics , Pregnancy
8.
Braz. j. med. biol. res ; 53(11): e9266, 2020. graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132491

ABSTRACT

The etiology of polycystic ovary syndrome (PCOS) is complex and the pathogenesis is not fully understood. Some studies have shown that dysregulation of ovarian granulosa cells may be related to abnormal follicles and excessive androgen in women with PCOS. Our team has also confirmed the high expression status of H19 in PCOS patients in the early stage. However, the relationship between H19 and miR-19b in the development of PCOS is still unknown. Therefore, we used bioinformatics to predict the binding sites of human H19 and miR-19b, and of miR-19b and CTGF genes. After the silencing and overexpression of H19, real-time polymerase chain reaction (PCR) was used to detect the expressions of H19, miR-19b, and CTGF. Western blotting was used to detect CTGF protein. Proliferation of KGN cells after H19 silencing was detected by CCK8. Flow cytometry was used to detect the apoptosis of KGN cells after H19 silencing. After the overexpression of H19, it was found that the expression of miR-19b gene decreased and the expression of CTGF increased, whereas silencing of H19 did the opposite. In addition, H19 could promote cell proliferation and decrease cell apoptosis. Finally, luciferase reporter assays showed that the 3′-end sequences of lncRNA H19 and CTGF contained the binding site of miR-19b. In conclusion, our study indicated that lncRNA H19 acted as a ceRNA to bind to miR-19b via a "sponge" to regulate the effect of CTGF on KGN cells, which may play a vital role in PCOS.


Subject(s)
Humans , Female , Polycystic Ovary Syndrome/genetics , Apoptosis , MicroRNAs/genetics , Cell Proliferation , Connective Tissue Growth Factor , RNA, Long Noncoding/genetics
9.
Arch. endocrinol. metab. (Online) ; 63(5): 501-508, Sept.-Oct. 2019. tab
Article in English | LILACS | ID: biblio-1038497

ABSTRACT

ABSTRACT Objective To investigate the association of the genetic variants of the folate metabolism genes (MTHFR C677T; MTHFR A1298C; MTR A2756G; MTRR A66G and RFC-1 A80G) with the development of polycystic ovary syndrome (PCOS). Subjects and methods This study included 203 women (99 women with PCOS and 104 controls). The genotyping was performed by PCR-RFLP. Chi-squared test and multiple logistic regression were used in the statistical analysis. Haplotype analysis was conducted using the SNPstat program. The results were presented in odds ratio (OR) and confidence interval of 95% (CI-95%), with a significance level of 5% (p ≤ 0.05). Results The genotypic distribution of the RFC-1 A80G polymorphism showed significant difference between the two groups, showing that the heterozygous genotype (AG genotype) was most frequent in controls. The polymorphic homozygous (GG genotype) of MTRR A66G polymorphism were most frequent in controls. The T-C haplotype MTHFR C677T and A1298C polymorphisms were more frequent in the control group (OR = 0.19; CI 95% — 0.04 to 0.93 e p = 0.042). The multivariate analysis evidenced that family history of PCOS was more frequent in the PCOS group (OR = 3.29; CI 95% — 1.48 to 7.31; p = 0.003). Conclusion In our casuistry, the polymorphic homozygous of MTRR A66G polymorphism gene and heterozygous of RFC-1 A80G polymorphism gene, the haplotype T-C C677T and A1298C polymorphisms of MTHFR gene, can be associated with protective factors for the disease.


Subject(s)
Humans , Female , Adult , Young Adult , Polycystic Ovary Syndrome/genetics , Polymorphism, Genetic/genetics , Folic Acid/genetics , Polycystic Ovary Syndrome/metabolism , Polymorphism, Restriction Fragment Length , Case-Control Studies , Risk Factors , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Folic Acid/metabolism , Genotype
10.
Rev. bras. ginecol. obstet ; 41(1): 37-43, Jan. 2019. tab
Article in English | LILACS | ID: biblio-1003512

ABSTRACT

Abstract Objective To evaluate the prevalence of metabolic syndrome (MetS) in the phenotypes of polycystic ovarian syndrome (PCOS). Methods This was a cross-sectional study involving 111 women aged between 18 and 39 years old diagnosed with PCOS, according to the Rotterdam Criteria, and grouped into four phenotypes: A: ovulatory dysfunction + hyperandrogenism + polycystic ovaries; B: ovulatory dysfunction + hyperandrogenism; C: hyperandrogenism + polycystic ovaries; D: ovulatory dysfunction + polycystic ovaries. To evaluate the presence of MetS, wemeasured serum triglyceride levels, HDL cholesterol, fasting blood glucose, blood pressure, and waist circumference. Results The prevalence of MetS found in this sample was 33.6%, and there was no statistically significant difference (p < 0.05) among the 4 phenotypes. However, phenotype D presented a significantly higher mean glucose level after fasting (93.6 mg/dL) and 2 hours after ingesting a solution with 75 g of anhydrous glucose (120 mg/dL), as well as the lowest mean level of high-density lipoprotein (HDL) cholesterol (44.7 mg/dL). The women in this group demonstrated a high prevalence of abdominal circumference ≥ 80 cm (68.2%), as well as the highest mean abdominal circumference (90.1 cm). Amongst the women with an abdominal circumference ≥ 80 cm, phenotype A increased approximately six-fold the chance of developing metabolic syndrome in relation to phenotype C. Conclusion The four phenotypes of PCOS demonstrated similar prevalence rates of metabolic syndrome; abdominal obesity presented a relevant role in the development of metabolic alterations, regardless of the phenotype.


Resumo Objetivo Avaliar a prevalência da síndromemetabólica nos fenótipos da síndrome do ovário policístico. Métodos Trata-se deum estudo transversal envolvendo 111 mulheres comidade entre 18 e39 anos com diagnóstico de síndrome do ovário policístico, segundo os critérios de Roterdã, e agrupadas em quatro fenótipos: A: Disfunção ovulatória + hiperandrogenismo + ovários policísticos;B: disfunçãoovulatória + hiperandrogenismo; C: hiperandrogenismo + ovários policísticos; D: disfunção ovulatória + ovários policísticos. Para avaliar a presença de síndrome metabólica, foram medidos os níveis séricos de triglicérides, colesterol HDL e glicemia de jejum, pressão arterial e circunferência da cintura. Resultados A prevalência de síndrome metabólica encontrada nesta amostra foi de 33,6%, e não houve diferença estatisticamente significativa (p < 0,05) entre os quatro fenótipos. Entretanto, o fenótipo D apresentou um nível médio de glicose significativamente mais alto após o jejum (93,6 mg/dL) e duas horas após a ingestão de uma solução com 75g de glicose anidra (120 mg/dL), bem como o menor nível médio de colesterol HDL (44,7 mg/dl). As mulheres deste grupo demonstraram alta prevalência de circunferência abdominal ≥ 80 cm (68,2%), bem como a maior média de circunferência abdominal (90,1 cm). Entre as mulheres com circunferência abdominal ≥ 80 cm, o fenótipo A aumentou em aproximadamente 6 vezes a chance de desenvolver síndrome metabólica em relação ao fenótipo C. Conclusão Os quatro fenótipos da síndrome do ovário policístico demonstraram taxas semelhantes de prevalência de síndrome metabólica; a obesidade abdominal apresentou papel relevante no desenvolvimento de alterações metabólicas, independentemente do fenótipo.


Subject(s)
Humans , Female , Adult , Young Adult , Polycystic Ovary Syndrome/complications , Metabolic Syndrome/etiology , Metabolic Syndrome/epidemiology , Phenotype , Polycystic Ovary Syndrome/genetics , Prevalence , Cross-Sectional Studies
11.
Rev. Assoc. Med. Bras. (1992) ; 64(11): 1017-1022, Nov. 2018. tab, graf
Article in English | LILACS | ID: biblio-976798

ABSTRACT

SUMMARY PURPOSE: To investigate the contribution of the deletion polymorphism and insertion (rs1799752) of the angiotensin converting enzyme (ACE) gene in the aetiology of Polycystic Ovarian Syndrome (PCOS). METHODOLOGY: 97 women diagnosed with PCOS who received care at the Gynaecology and Obstetrics clinic of the Hospital das Clínicas of UFTM, participated in this study. The control group consisted of 94 women. All participants were submitted to the collection of 10 mL of whole blood and the genomic DNA was obtained by the saline extraction method. The genotyping of the samples was performed by means of the Polymerase Chain Reaction (PCR). The statistics analyses were performed by descriptive analysis, univariate analysis and logistic regression model. The results were presented in odds ratio (OR) and confidence interval of 95% (CI-95%), with a significance level of 5% (p≤0.05). RESULTS: There were no statistical differences between patients and controls for the genotypic (χ2 = 1.52, p = 0.47) and allelic frequencies (χ2 = 0.21, p = 0.76). The distribution of the genotypic frequency is not in HWE for patients (χ2 = 18.80, p <0.05) and for controls (χ2 = 6.85, p <0.05). In relation to the risk factors for the syndrome, the history of familial PCOS is more frequent between women with the syndrome. CONCLUSION: In the study population, there was no association between I/D polymorphism of the ACE gene and PCOS.


RESUMO OBJETIVO: Investigar a contribuição do polimorfismo de deleção e inserção (rs1799752) do gene enzima conversora de angiotensina (ECA) na etiologia da Síndrome dos Ovários Policísticos (SOP). MÉTODOS: Participaram deste estudo 97 mulheres diagnosticadas com SOP, atendidas no ambulatório de Ginecologia e Obstetrícia do Hospital de Clínicas da UFTM. O grupo controle foi constituído por 94 mulheres. Todas as participantes foram submetidas à coleta de 10 mL de sangue total e o DNA genômico foi obtido pelo método de extração salina. A genotipagem das amostras foi realizada por meio da Reação da Cadeia da Polimerase (PCR). A análise estatística foi realizada por análises descritivas, análise univariada e modelo de regressão logística. Os resultados foram apresentados em odds ratio (OR) e intervalo de confiança de 95% (IC - 95%). Foi considerado o nível de significância de 5% (p≤0,05). RESULTADOS: Não foram observadas diferenças estatísticas entre pacientes e controles para as frequências genotípicas (χ2=1,52; p=0,47) e alélicas (χ2=0,21; p=0,76). A distribuição da frequência genotípica não está em equilíbrio de HWE para as pacientes (χ2=18,80; p<0,05) e para controles (χ2=6,85; p<0,05). Em relação aos fatores de risco para a síndrome, a história familial de SOP é mais frequente entre as pacientes. CONCLUSÃO: Na casuística estudada não há associação do polimorfismo I/D do gene ACE e SOP.


Subject(s)
Humans , Female , Polycystic Ovary Syndrome/genetics , Polymorphism, Genetic , Peptidyl-Dipeptidase A/genetics , Case-Control Studies , Polymerase Chain Reaction , Genetic Predisposition to Disease/genetics , Gene Frequency , Genotype
12.
Arch. endocrinol. metab. (Online) ; 62(3): 352-361, May-June 2018. tab, graf
Article in English | LILACS | ID: biblio-950067

ABSTRACT

ABSTRACT Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder that affects 5-20% of reproductive age women. PCOS clinical symptoms include hirsutism, menstrual dysfunction, infertility, obesity and metabolic syndrome. There is a wide heterogeneity in clinical manifestations and metabolic complications. The pathogenesis of PCOS is not fully elucidated, but four aspects seem to contribute to the syndrome to different degrees: increased ovarian and/or adrenal androgen secretion, partial folliculogenesis arrest, insulin resistance and neuroendocrine axis dysfunction. A definitive etiology remains to be elucidated, but PCOS has a strong heritable component indicated by familial clustering and twin studies. Genome Wide Association Studies (GWAS) have identified several new risk loci and candidate genes for PCOS. Despite these findings, the association studies have explained less than 10% of heritability. Therefore, we could speculate that different phenotypes and subphenotypes are caused by rare private genetic variants. Modern genetic studies, such as whole exome and genome sequencing, will help to clarify the contribution of these rare genetic variants on different PCOS phenotypes. Arch Endocrinol Metab. 2018;62(3):352-61


Subject(s)
Humans , Female , Polycystic Ovary Syndrome/genetics , Phenotype
13.
Clinics ; 72(8): 510-514, Aug. 2017. tab, graf
Article in English | LILACS | ID: biblio-890718

ABSTRACT

OBJECTIVES: Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol. METHODS: A single injection of testosterone propionate (1.25 mg) (n=10) or estradiol benzoate (0.5 mg) (n=10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n=10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis. RESULTS: Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-β and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-α genes and upregulation of the gene that encodes the kisspeptin receptor. CONCLUSIONS: Testosterone- and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosterone- and estradiol-induced polycystic ovary syndrome rats.


Subject(s)
Animals , Female , Gonadotropin-Releasing Hormone/analysis , Hypothalamus/chemistry , Kisspeptins/analysis , Luteinizing Hormone/metabolism , Pituitary Gland/metabolism , Polycystic Ovary Syndrome/chemistry , Disease Models, Animal , Down-Regulation , Estradiol , Gene Expression , Gonadotropin-Releasing Hormone/genetics , Hypothalamus/metabolism , Kisspeptins/genetics , Phenotype , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/metabolism , Rats, Wistar , Real-Time Polymerase Chain Reaction , Receptors, Androgen/analysis , Receptors, Estrogen/analysis , Testosterone , Up-Regulation
14.
Rev. méd. Chile ; 145(7): 907-915, jul. 2017. tab, graf
Article in Spanish | LILACS | ID: biblio-902563

ABSTRACT

Polycystic ovarian syndrome (PCOS) is an endocrine and metabolic dysfunction, highly prevalent in women in their reproductive years. Hyperandrogenism, oligo-ovulation, polycystic ovarian morphology are the main features of this syndrome. PCOS is a genetic disorder with a multifactorial etiology and has a strong link with environmental components. It is frequently associated with obesity and insulin resistance. Recently, epigenetic mechanisms have been involved in the pathogenesis of PCOS. Several studies showed that methylation in DNA and miRNAs is altered in women with PCOS in blood, serum, adipose tissue, granulose cells and theca. This evidence indicates that women with PCOS have a different epigenetic regulation, which might be triggered by an adverse intrauterine environment or by postnatal environmental elements such as diet and or obesity.


Subject(s)
Humans , Female , Polycystic Ovary Syndrome/genetics , Gene Expression Regulation, Neoplastic/genetics , DNA Methylation/genetics , MicroRNAs/genetics , Epigenesis, Genetic/genetics
15.
Rev. cuba. endocrinol ; 26(1): 21-32, ene.-abr. 2015.
Article in Spanish | LILACS, CUMED | ID: lil-740904

ABSTRACT

Introducción: La existencia de manifestaciones del síndrome de ovarios poliquísticos en familiares de primer grado de pacientes con ese síndrome, ha permitido sospechar la participación de un componente genético en su patogénesis.Objetivos: identificar características clínicas del síndrome de ovarios poliquísticos en familiares de primer grado de mujeres con ese síndrome, e identificar si existe agregación familiar para el síndrome de ovarios poliquísticos.Métodos: se realizó un estudio descriptivo transversal, en 28 mujeres con síndrome de ovarios poliquísticos y 28 mujeres sin él, todas entre 18 y 49 años. Se les realizó un interrogatorio, examen físico, así como un árbol genealógico detallado buscando familiares de primer grado con estigmas del síndrome. Se calcularon las estadísticas descriptivas de todas las variables. Se realizó un estudio de agregación familiar general, y luego particular de casos y controles. Se calculó el OR con un 95 pr ciento de intervalo de confianza, como estadígrafo que mide la magnitud de asociación, y se estimó el riesgo de padecer la enfermedad si existía el antecedente familiar. En todos los casos se consideró un nivel de significación de p< 0,05.Resultados: 19 de los familiares de primer grado de las mujeres con síndrome de ovarios poliquísticos tuvieron hirsutismo, y solo 3 de los controles (p= 0,00); en el caso de las alteraciones menstruales, 16 de los familiares de primer grado de parentesco de los casos, manifestó este trastorno, y en los controles fueron solamente 7 (p= 0,04). La calvicie de aparición en edades tempranas está presente en 16 de los hombres con parentesco de primera línea filial de las mujeres afectadas, y solo 3 se observaron en los controles (p= 0,03). De los 48 familiares de primer grado estudiados de las mujeres con síndrome de ovarios poliquísticos, el 37,50 por ciento tenían criterios del síndrome. En el estudio de agregación familiar se estimó una posibilidad de 14,27 veces mayor de padecer la enfermedad, si se es familiar de un paciente afectado. Conclusiones: los estigmas de síndrome de ovarios poliquísticos y el mismo como tal son frecuentes en los familiares de primer grado de mujeres con él, y se demostró que existe agregación familiar(AU)


Introduction: Manifestations of polycystic ovary syndrome in first-degree relatives of patients suffering this disorder have allowed suspecting the involvement of a genetic component in its pathogenesis.Objectives: to identify the clinical characteristics of the polycystic ovary syndrome in the first-degree relatives of women with this syndrome and to detect the familial clustering for the polycystic ovary syndrome. Methods: cross-sectional and descriptive study of 28 females with polycystic ovary syndrome and 28 syndrome-free females aged 18 to 49 years-old. They were questioned and physically examined, and a detailed family tree was created to look for first-degree relatives with the syndrome stigma. Summary statistics for all variables were estimated. A general familial clustering study in addition to a case and control study were performed. The 95 percent CI odds ratio was estimated as an statistic that measures the range of association. The risk of suffering the disease in case of familial background was also assessed. The level of significance was p< 0.05 in every case. Results: nineteen of the first-degree relatives of women with the polycystic ovary syndrome had hirsutism and just three of the controls (p= 0.00). Regarding the menstrual alterations, this disorder manifested itself in 16 of the first degree relatives and in 7 of the controls(p= 0.04). Baldness appears at early ages in 16 of first-degree male relatives and only 3 were found in the controls (p= 0.03). Of 48 studied first-degree relatives of women with polycystic ovary syndrome, 37.50 percent met the syndrome criteria. The familial clustering study estimated that the relative of a patient is 14.27 more likely to suffer the disease. Conclusions: polycystic ovary syndrome stigmas and the syndrome as such are frequent in the first-degree relatives of women suffering this disorder and it was proved that familiar clustering does exist(AU)


Subject(s)
Humans , Female , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/epidemiology , Epidemiology, Descriptive , Cross-Sectional Studies/methods , Pedigree
16.
Clinics ; 69(3): 179-184, 3/2014. tab
Article in English | LILACS | ID: lil-703600

ABSTRACT

OBJECTIVES: We aimed to investigate whether glucocorticoid receptor gene polymorphisms are associated with clinical and metabolic profiles in patients with polycystic ovary syndrome. Polycystic ovary syndrome is a complex endocrine disease that affects 5-8% of women and may be associated with metabolic syndrome, which is a risk factor for cardiovascular disease. Cortisol action and dysregulation account for metabolic syndrome development in the general population. As glucocorticoid receptor gene (NR3C1) polymorphisms regulate cortisol sensitivity, we hypothesized that variants of this gene may be involved in the adverse metabolic profiles of patients with polycystic ovary syndrome. METHOD: Clinical, metabolic and hormonal profiles were evaluated in 97 patients with polycystic ovary syndrome who were diagnosed according to the Rotterdam criteria. The alleles of the glucocorticoid gene were genotyped. Association analyses were performed using the appropriate statistical tests. RESULTS: Obesity and metabolic syndrome were observed in 42.3% and 26.8% of patients, respectively. Body mass index was positively correlated with blood pressure, triglyceride, LDL-c, total cholesterol, glucose and insulin levels as well as HOMA-IR values and inversely correlated with HDL-c and SHBG levels. The BclI and A3669G variants were found in 24.7% and 13.4% of alleles, respectively. BclI carriers presented a lower frequency of insulin resistance compared with wild-type subjects. CONCLUSION: The BclI variant is associated with a lower frequency of insulin resistance in women with polycystic ovary syndrome. Glucocorticoid gene polymorphism screening during treatment of the syndrome may be useful for identifying subgroups of at-risk patients who would benefit the most from personalized treatment. .


Subject(s)
Adult , Female , Humans , Young Adult , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/metabolism , Polymorphism, Genetic/genetics , Receptors, Glucocorticoid/genetics , Alleles , Body Mass Index , Cholesterol , Fluoroimmunoassay , Gene Frequency , Genes, bcl-1/genetics , Hypertension/genetics , Hypertension/metabolism , Insulin Resistance/genetics , Metabolic Syndrome/genetics , Metabolic Syndrome/metabolism , Obesity/genetics , Obesity/metabolism , Polymerase Chain Reaction , Risk Factors , Statistics, Nonparametric , Time Factors
17.
Rev. cuba. endocrinol ; 22(3): 255-265, sep.-dic. 2011.
Article in Spanish | LILACS, CUMED | ID: lil-615041

ABSTRACT

El síndrome de ovarios poliquísticos es el trastorno endocrino que más afecta la esfera reproductiva de la mujer en la edad fértil, sus causas se desconocen con exactitud, pero la mayoría de los expertos coinciden en plantear que es una entidad multifactorial, en la que los factores genéticos cada vez cobran mayor importancia. En los últimos años se han identificado varios genes involucrados en los procesos patogénicos de este síndrome, y dentro de estos, los más importantes son aquellos que codifican para enzimas de la esteroidogénesis, para el receptor de insulina y otras hormonas relacionadas con la acción de la insulina, así como las gonadotropinas y sus receptores, aspectos sobre los cuales trata la siguiente revisión(AU)


The syndrome of polycystic ovaries is the endocrine disorder involving more the reproductive sphere of the woman in fertile age, its causes are unknown with accuracy, but most of experts coincide in propose that it is a multifactor entity where the genetic factor more and more have a great significance. In past years, it has been possible to identify some genes involved in the pathogenic processes of this syndrome and among the more important are included those codifying for enzymes of the steroidogenesis, for the insulin receptor and other hormones related to the insulin action, as well as the gonadotropins and its receptors, features that are the aim of present review(AU)


Subject(s)
Humans , Polycystic Ovary Syndrome/genetics , Primary Ovarian Insufficiency/genetics , Gonadotropins/adverse effects
18.
Rev. bras. ginecol. obstet ; 32(7): 334-339, jul. 2010. tab
Article in Portuguese | LILACS | ID: lil-567966

ABSTRACT

OBJETIVO: avaliar as características clínicas e laboratoriais de parentes de primeiro grau do sexo masculino de pacientes com diagnóstico confirmado de síndrome de ovários policísticos (SOP) e comparar os achados com um grupo controle sem história familiar de SOP. MÉTODOS: foram selecionados aleatoriamente 28 homens com idade entre 18 e 65 anos que possuíam parentesco de primeiro grau com mulheres diagnosticadas com SOP e 28 controles pareados por idade, cintura e índice de massa corporal (IMC). RESULTADOS: homens com parentesco de 1º grau com mulheres com SOP comparados ao Grupo Controle apresentaram níveis mais elevados de triglicerídeos (189,6±103,1 versus 99,4±37,1; p<0,0001), HOMA-IR (Homeostase Model Assesment) (3,5±9,1 versus 1,0±1,0; p=0,0077) e glicemia (130,1±81,7 versus 89,5±7,8; p=0,005), além de menores níveis da globulina ligadora de hormônios sexuais (SHBG) (23,8±13,8 versus 31,1±9,1; p=0,003). Os níveis de SHBG se correlacionaram independentemente com os níveis de triglicérides. Os parentes de 1º grau também apresentavam mais sinais clínicos de hiperandrogenismo. CONCLUSÕES: parentes de primeiro grau do sexo masculino das pacientes com SOP apresentam maior grau de dislipidemia e de resistência à insulina, além de níveis mais baixos de SHBG com mais sinais clínicos de hiperandrogenismo. Esses achados sugerem que a resistência à insulina pode ter origem hereditária em indivíduos com história familiar de SOP, independentemente de parâmetros antropométricos.


PURPOSE: to evaluate clinical and laboratory characteristics of first-degree male relatives of patients with a confirmed diagnosis of polycystic ovary syndrome (PCOS) and to compare the findings with a control group with no family history of PCOS. METHODS: we randomly selected 28 male individuals aged 18 to 65 years who were first-degree relatives of women diagnosed with PCOS and 28 controls matched for age, waist and body mass index (BMI). RESULTS: men with 1st degree kinship with women with PCOS had higher levels of triglycerides (189.6±103.1 versus 99.4±37.1, p<0.0001), Homeostasis Model Assessment (HOMA-IR) (3.5±9.1 versus 1.0±1.0, p=0.0077) and glucose (130.1±81.7 versus 89.5±7.8, p=0.005), and lower levels of sex hormone binding globulin (SHBG) (23.8±13.8 versus 31.1±9.1, p=0.003). SHBG levels correlated independently with triglyceride levels. These individuals also had more clinical signs of hyperandrogenism. CONCLUSIONS: male individuals who are first-degree relatives of patients with PCOS have a higher degree of dyslipidemia and insulin resistance, lower levels of SHBG, and more evident clinical signs of hyperandrogenism. These findings suggest that insulin resistance may be of hereditary origin in individuals with a family history of PCOS regardless of anthropometric parameters.


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Body Mass Index , Hyperandrogenism/blood , Polycystic Ovary Syndrome , Waist Circumference , Waist-Hip Ratio , Hyperandrogenism/genetics , Polycystic Ovary Syndrome/genetics , Waist Circumference/genetics
19.
Rev. chil. obstet. ginecol ; 75(2): 124-132, 2010. tab, graf
Article in Spanish | LILACS | ID: lil-565388

ABSTRACT

Antecedentes: El síndrome de ovario poliquístico (SOP) es la endocrinopatía más frecuente en la mujer de edad reproductiva, de etiología incierta y presentación clínica heterogénea. Su diagnóstico y defnición es aún controversial. La introducción de los criterios del Consenso de Rotterdam generó nuevos fenotipos al incorporar la ecografía transvaginal como elemento diagnóstico, aumentando aún más la heterogeneidad del síndrome. Objetivo: Determinar en una cohorte consecutiva de 102 pacientes con diagnóstico de SOP, su frecuencia, las características clínicas, hormonales y metabólicas, de los cuatro fenotipos posibles según Rotterdam. Resultados: Fenotipo A 62 por ciento, Fenotipo B 21 por ciento, Fenotipo C 9 por ciento y Fenotipo D 8 por ciento. El síndrome metabólico se presentó en 29 por ciento de las pacientes, siendo mayor en los fenotipos A (30 por ciento) y B (43 por ciento) que en los fenotipos C (11 por ciento) y D (13 por ciento). El 82 por ciento presentaba sobrepeso, siendo signifcativamente mayor en los fenotipos A (88 por ciento) y B (90 por ciento). Hubo diferencias signifcativas al comparar las variables puntaje de hir-sutismo, SHBG, testosterona total, IAL, volumen ovárico, colesterol total, colesterol HDL, colesterol LDL y glicemia en ayuno. No existieron diferencias signifcativas entre los grupos al comparar las variables edad, IMC, DHEA-SO4 y triglicéridos. Conclusión: El consenso de Rotterdam agruparía a diferentes fenotipos en un mismo síndrome, que podrían representar distintos grados de severidad de una misma enfermedad. Se desconoce si estos fenotipos poseen los mismos riesgos a largo plazo y sería apresurado tratarlos como una misma entidad.


Background: Policystic ovary syndrome (PCOS) is a very common endocrine disease in women of reproductive age, of uncertain etiology and heterogeneous clinical presentation. The introduction of the Rotterdams Consensus criteria generated new phenotypes by incorporating transvaginal ultrasound, thus increasing the heterogenity of PCOS. Objectives: To determine in a cohort of 102 patients with the diagnosis of PCOS the prevalence, clinical, hormonal and metabolic profle according to Rotterdam. Results: It was determined the Phenotype A 62 percent Phenotype B 21 percent, Phenotype C 9 percent and Phenotype D 8 percent of the patients. The metabolic syndrome was present in 29 percent of the PCOS patients, being it more frequent in the phenotypes A (30 percent) and B (43 percent) than C (11 percent) and D (13 percent). The 82 percent of the patients were overweigth, especially in the phenotypes A (88 percent) and B (90 percent). Also, statistically signifcant differences were observed when comparing the variables score of hirsutism, free androgen index, total testosterone, HDL cholesterol SHBG, ovarian volume, total cholesterol, glycemia and LDL cholesterol. There were no signifcant differences between the groups to compare variables such as age, BMI, DHEA and triglycerides. Conclusion: These fndings indicate that the consensus of Rotterdam would agroup different phenotypes in the same syndrome and that it may represent different degrees of severity of the same disease. Even though, we do not know if these phenotypes posses the same health risks, therefore it is soon to manage the phenotypes as equal entities.


Subject(s)
Humans , Female , Adult , Phenotype , Polycystic Ovary Syndrome/diagnosis , Polycystic Ovary Syndrome/epidemiology , Polycystic Ovary Syndrome/genetics , Body Mass Index , Chile/epidemiology , Cardiovascular Diseases/etiology , Hyperandrogenism/epidemiology , Hyperandrogenism/genetics , Hirsutism/epidemiology , Hirsutism/genetics , Obesity/epidemiology , Obesity/genetics , Retrospective Studies , Risk Assessment , Metabolic Syndrome/epidemiology , Metabolic Syndrome/genetics , Polycystic Ovary Syndrome/classification
20.
Rev. Soc. Argent. Endocrinol. Ginecol. Reprod ; 16(1): 26-33, mayo 2009. graf
Article in Spanish | LILACS, BINACIS | ID: biblio-1171274

ABSTRACT

El síndrome de poliquistosis ovárica (PCOs) es un desorden multisistémico heterogéneo de etiología aun no totalmente definida y comúnmente asociado a obesidad e insulino-resistencia. La insulino-resistencia y la consecuente hiperinsulinemia juegan un rol clave en la patogénesis de PCOs. La importancia de este rol clave en PCOs ha sido recientemente confirmada por estudios con drogas insulino-sensibilizantes que restauran la función ovárica y disminuyen la biosíntesis y secreción de andrógenos en ovario, estableciendo una relación causalidad desde la insulino-resistencia hacia el desorden en el eje hipotálamo-hipófisi-gonadal. PCOs desde el punto de vista genético, es considerado un síndrome poligénico de herencia no mendeliana como lo son la diabetes tipo 2, la obesidad, la hipertensión arterial, etc. La segregación familiar tanto del rasgo metabólico como del hiperandrogenismo funcional sugiere una base hereditaria. Este desorden, se desarrolla por la combinación de factores de riesgo genéticos y factores ambientales desencadenantes. En PCOs se considera que las vías metabólicas principalmente afectadas serían: la síntesis de hormonas esteroideas, la síntesis y acción de la insulina y otros caminos metabólicos involucrados en diferentes mecanismos de regulación. Teniendo en cuenta las vías metabólicas afectadas, se postulan como genes candidatos a aquellos involucrados en los mecanismos de síntesis o regulación mencionados...


Subject(s)
Female , Humans , Polycystic Ovary Syndrome/etiology , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/metabolism
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