Polymorphisms rs2010963 and rs833061 of the VEGF gene in polycystic ovary syndrome.

OBJECTIVE: The polycystic ovary syndrome is the most common endocrine disorder, characterized by the dysregulation of ovarian angiogenesis. This alteration can be related to changes in the activities of the vascular endothelial growth factor (VEGF) gene. Single-nucleotide polymorphisms have been observed in the promoter, intronic, and untranslated regions of the VEGF gene, and several studies have suggested that these polymorphisms may be associated with the risk of polycystic ovary syndrome. This study aimed to investigate the association between rs2010963 and rs833061 polymorphisms and haplotypes of VEGF in the etiology of polycystic ovary syndrome. METHODS: A total of 210 women, 102 diagnosed with polycystic ovary syndrome and 108 controls, participated in this study. The genotyping of the samples was performed by PCR-RFLP and real-time PCR for rs2010963 and rs833061 polymorphisms, respectively. The statistical analyses were performed by the chi-square test and logistic regression model. RESULTS: The clinical characteristics of the patients showed that 75.8% of the patients did not become pregnant, 36.3% had a family history of polycystic ovary syndrome, 58.6% were obese, and about 60% had clinical characteristics of hyperandrogenism. There were no associations between the distribution of rs2010963 (OR 1.24; 95%CI 0.60-2.57; p=0.56) and rs833061 (OR 0.78; 95%CI 0.32-1.92; p=0.59) in patients and controls. CONCLUSIONS: The patients with polycystic ovary syndrome have similar rates of VEGF polymorphisms rs2010963 and rs833061 on the general population.

Polymorphisms rs2010963 and rs833061 of the VEGF gene in polycystic ovary syndrome

SUMMARY OBJECTIVE: The polycystic ovary syndrome is the most common endocrine disorder, characterized by the dysregulation of ovarian angiogenesis. This alteration can be related to changes in the activities of the vascular endothelial growth factor (VEGF) gene. Single-nucleotide polymorphisms have been observed in the promoter, intronic, and untranslated regions of the VEGF gene, and several studies have suggested that these polymorphisms may be associated with the risk of polycystic ovary syndrome. This study aimed to investigate the association between rs2010963 and rs833061 polymorphisms and haplotypes of VEGF in the etiology of polycystic ovary syndrome. METHODS: A total of 210 women, 102 diagnosed with polycystic ovary syndrome and 108 controls, participated in this study. The genotyping of the samples was performed by PCR-RFLP and real-time PCR for rs2010963 and rs833061 polymorphisms, respectively. The statistical analyses were performed by the chi-square test and logistic regression model. RESULTS: The clinical characteristics of the patients showed that 75.8% of the patients did not become pregnant, 36.3% had a family history of polycystic ovary syndrome, 58.6% were obese, and about 60% had clinical characteristics of hyperandrogenism. There were no associations between the distribution of rs2010963 (OR 1.24; 95%CI 0.60-2.57; p=0.56) and rs833061 (OR 0.78; 95%CI 0.32-1.92; p=0.59) in patients and controls. CONCLUSIONS: The patients with polycystic ovary syndrome have similar rates of VEGF polymorphisms rs2010963 and rs833061 on the general population.

Screening of six polymorphisms related with folate metabolism in parents of individuals with Down syndrome.

OBJECTIVE: The study aim to investigate MTHFR C677T, MTHFR A1298C, RFC1 A80G, MTR A2756G, CBS 844ins68, MTRR A66G polymorphisms in Down syndrome (DS) parents. METHODS: Polymorphisms were evaluated in 35 mothers and 24 fathers of individuals with free trisomy of chromosome 21 confirmed by karyotype. The control group included 26 mothers and 26 fathers who had no children with DS. The molecular analysis was performed by polymerase chain reaction and restriction fragment length polymorphism (reaction chain polymerase restriction fragment length polymorphism) or polymerase chain reaction. The χ2 test (chi-square) was used to compare allele's differences among the study and the control group. Hardy-Weinberg equilibrium model was performed by χ2 testing. Multiple logistic regression models and binary logistic regression used to determine the association between polymorphisms and parental DS risk. RESULTS: This study did not reveal any significant difference in frequencies of polymorphisms. The haplotype analysis did not reveal linkage disequilibrium. The logistic regression analysis did not demonstrate differences between the groups. However, the binary logistic regression showed a higher frequency of the polymorphic homozygote genotype in DS parent group to codominant and dominant model in the RFC1 A80G. CONCLUSION: In conclusion, although the screening results were significant only to the RFC1 A80G polymorphism, the other determinations of the genetic factors associated with abnormal chromosome segregation could be helpful in future studies, including other polymorphisms involved in folate metabolism.

Polymorphisms of the GSTT1 and GSTM1 genes in polycystic ovary syndrome.

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.

Polymorphisms of the GSTT1 and GSTM1 genes in polycystic ovary syndrome

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.

Contribution of rs1799998 polymorphism in CYP11B2 gene in susceptibility to preeclampsia / Contribuição do polimorfismo rs1799998 no gene CYP11B2 na suscetibilidade à pré-eclampsia

Abstract Objectives: the present study aimed to evaluate the association between the rs1799998 polymorphism of the CYP11B2 gene and the susceptibility to preeclampsia (PE) in a Brazilian population. Methods: the study group comprised 61 women who were diagnosed with PE. The control group included 116 women who did not show changes in their blood pressure levels during their pregnancies. The rs1799998 polymorphism of the CYP11B2 gene was amplified by allele-specific polymerase chain reaction (PCR). A multiple logistic regression analysis was performed using the SNPStat program to evaluate the risk of the CYP11B2 gene rs1799998 polymorphism contributing to PE. Results: the PE group had the following genotypes: 1.64% CC, 91.80% CT, and 6.56% TT. In the control group, the observed genotypic frequencies were: 11% CC, 73% CT, and 16% TT. The genotypic frequency distribution did not fit the Hardy Weinberg Equilibrium (HWE) in either study group. The multiple logistic regression analysis showed a statistically significant difference for the rs1799998 polymorphism in the recessive model. Conclusion: the results suggest an association between the recessive model of C/C genotype of the rs1799998 polymorphism of the CYP11B2 gene and susceptibility to PE.

Resumo Objetivos: avaliar a associação entre o polimorfismo rs1799998 do gene CYP11B2 e a suscetibilidade à PE em uma população brasileira. Métodos: participaram desse estudo 61 mulheres com PE e 116 mulheres normotensas. O polimorfismo rs1799998 do gene CYP11B2 foi amplificado por PCR alelo-específica. O risco do polimorfismo rs1799998 do gene CYP11B2 contribuir com a PE foi avaliado pela análise de regressão logística múltipla. Resultados: as frequências genotípicas observadas foram 1.64% CC, 91.80% CT e 6.56% TT no grupo PE e 11%CC, 73%CT e 16%TT grupo controle. A distribuição da frequência genotípica não estava em Equilíbrio de Hardy Weinberg em nenhum dos grupos estudados. A análise de regressão logística múltipla demonstrou diferença estatisticamente significativa para o polimorfismo rs1799998 no modelo recessivo. Conclusão: o presente trabalho sugere associação do genótipo C/C no modelo recessivo, do polimorfismo rs1799998 do gene CYP11B2 com a suscetibilidade a PE.

Interferon-gamma signaling is downregulated in peripheral blood mononuclear cells from asthma patients / A sinalização de interferon-gama é diminuída em células mononucleares do sangue periférico de pacientes asmáticos

Introduction: Interferon-gamma (IFN-g) signaling is mediated by crosstalk of receptors, such as IFN-g receptor 1 (IFN-g R1), transcription factors, such as signal transducer and activator of transcription 1 (STAT1) and suppressors of cytokine signaling 1 (SOCS1). Here, we evaluated the role of IFN-g signaling in peripheral blood mononuclear cells (PBMCs) from asthma patients and control individuals. Methods: PBMCs from adult healthy nonasthmatic controls (n = 12; male and female, 18-60 years old) and patients diagnosed with asthma (n = 18; male and female, 18-60 years old) were stimulated with IFN-g (0.25, 0.5 and/or 1.0 ng/mL) and, after 24h, the production of CXC motif chemokine 10 (CXCL10) was evaluated (by enzyme linked immunosorbent assay) as well as the expression of IFN-g R1, STAT1 (both by flow cytometry assay) and SOCS1 (by real-time qPCR assay). Results: CXCL10 production was reduced in a dose-dependent manner in PBMCs from asthma patients stimulated with IFN-g when compared to control individuals. While IFN-g induced an increase in IFN-g R1 expression and phosphorylated STAT1 (pSTAT1) activation in PBMCs from the control group, a reduction in both IFN-g R1 and pSTAT1 was observed in PBMCs from asthma patients. IFN-g increased SOCS1 mRNA expression in PBMCs from asthma patients when compared to IFN-g-stimulated cells from control individuals. Conclusion: Taken together, our results demonstrated that IFN-g signaling is downregulated in asthma patients.

Introdução: A sinalização de interferon-gama (IFN-g) é mediada por receptores, como o receptor 1 de IFN-gama (IFN-gR1), fatores de transcrição, como o transdutor de sinal e o ativador de transcrição 1 (STAT1) e supressores de sinalização de citocina 1 (SOCS1). Neste trabalho, avaliamos o papel da sinalização de IFN-g em células mononucleares do sangue periférico (PBMCs) de indivíduos com asma e controle. Métodos: Células mononucleares do sangue periférico (PBMCs) de adultos saudáveis e não asmáticos (n = 12, homens e mulheres, 18-60 anos) e pacientes diagnosticados com asma (n = 18, homens e mulheres, 18-60 anos) foram estimuladas com IFN-g (0,25, 0,5 e/ou 1,0 ng/mL) e após 24 horas a produção de CXCL10 foi avaliada por ensaio de imunoabsorção enzimática (ELISA), bem como o receptor 1 de IFN-g (IFN-g R1). Também foram avaliadas as expressões do transdutor de sinal e ativador da transcrição 1 (STAT1) (por citometria de fluxo) e supressor de expressão de sinalização de citocinas 1 (SOCS1) (por ensaio qPCR em tempo real). Resultados: A produção de CXCL10, uma quimiocina induzida por IFNg, foi reduzida de maneira dependente da dose em PBMCs de pacientes com asma estimulados com IFN-g (0,25-1,0 ng/mL) quando comparado ao grupo controle. Enquanto IFN-g induziu um aumento da expressão de IFN-g R1 e ativação da fosforilação de STAT1 (pSTAT1) em PBMCs do grupo controle, uma redução de ambas (IFN-g R1 e pSTAT1) foi observada em PBMCs de pacientes com asma. O IFN-g aumentou as PBMCs de expressão do mRNA de SOCS1 de pacientes com asma quando comparado às células estimuladas por IFN-g do controle. Conclusão: Em conjunto, nossos resultados demonstraram que a sinalização de IFN-g é sub-regulada em pacientes com asma.

Can the genetic polymorphisms of the folate metabolism have an influence in the polycystic ovary syndrome?

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.

Can the genetic polymorphisms of the folate metabolism have an influence in the polycystic ovary syndrome?

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.

Haplotype analysis of VEGF gene polymorphisms in polycystic ovary syndrome.

This study evaluated the association of polymorphisms of VEGF (endothelial vascular growth factor) gene + 936C/T (rs3025039), 1154 G/A (rs 1570360) and -2578 C/A (rs 699947) in patients with polycystic ovary syndrome (PCOS) and to perform the haplotypes formed by the alleles in the Brazilian population. A total of 110 women without PCOS and 112 women with PCOS were included in the study. Genotyping analyses were performed using the PCR-RFLP assays (rs 3025039 and rs 699947) and by allelic discrimination using the real-time PCR technique (rs 1570360). In the univariate analysis, we observed a significant difference between the groups for the polymorphism rs 1570360 and this polymorphism presented statistical differences between the groups for the recessive model (p = .04). The frequency of the T-G-C haplotype showed a statistically significant difference between women with PCOS and controls (p = .05). The -2578 A/C polymorphism was more frequent in the control group, which may be associated with a protective characteristic for the PCOS manifestation. In the sample analysis, polymorphism rs 1570360 is associated with PCOS and the T-G-C haplotype could be associated with protective factors.

Polycystic ovarian syndrome: rs1799752 polymorphism of ACE gene.

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.

Polycystic ovarian syndrome: rs1799752 polymorphism of ACE gene

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.

Investigation of rs1800469 and rs1800468 Polymorphisms of the TGF-β 1 Gene in Women with Pre-eclampsia / Investigação dos Polimorfismos rs1800469 e rs1800468 do Gene TGF-β 1 em Mulheres com Pré-eclâmpsia

Abstract Objectives: to verify the contribution of polymorphisms rs1800469 and rs1800468 of the TGF-β1 gene and the risk factors for the pre-eclampsia development. Methods: this is a case-control study with 257 women from the Uberaba region of Minas Gerais were selected, 88 of them were in the pre-eclampsia group and 169 in the control group. Genotyping was performed by allelic discrimination using the real-time PCR technique. The odds ratio and the 95% confidence interval were used to evaluate the probability of the polymorphisms studied contributing for the pre-eclampsia development. The logistic regression analysis was performed to evaluate the relation among family recurrence, smoking, primiparity and the presence of polymorphic alleles and susceptibility of preeclampsia. Results: no association was found between polymorphisms rs1800469 and rs1800468 of the TGF-β1 gene and pre-eclampsia. The logistic regression analysis was statistically significant for family recurrence, showing that women with a family history of pre-eclampsia and primiparity are at an increased risk of developing the disease. Conclusions: no association was found between polymorphisms rs1800469 and rs1800468 of the TGF-β1 and pre-eclampsia gene. Factors such as family history and primiparity were associated to the risk of developing pre-eclampsia.

Resumo Objetivos: verificar a contribuição dos polimorfismos rs1800469 e rs1800468 do gene TGF-β1 e de fatores de risco para o desenvolvimento de PE. Métodos: trata-se de um estudo caso-controle, onde foram selecionadas 257 mulheres, da região de Uberaba, Minas Gerais, sendo 88 do grupo PE e 169 controles. A genotipagem foi realizada por discriminação alélica através da técnica de PCR em tempo real. Odds ratio e o intervalo de confiança de 95% foram usados para avaliar a probabilidade dos polimorfismos estudados contribuírem com o desenvolvimento de PE. A análise de regressão logística foi realizada para avaliar a relação entre recorrência familiar, tabagismo, primiparidade e presença dos alelos polimórficos e a suscetibilidade a PE. Resultados: não foi observada associação entre os polimorfismos rs1800469 e rs1800468 do gene TGF-β1 e PE. A análise de regressão logística foi estatisticamente significativa para recorrência familiar, mostrando que mulheres com histórico familiar de PE e mulheres primigestas possuem risco aumentado de desenvolver a doença. Conclusões: não foi encontrada associação entre os polimorfismos rs1800469 e rs1800468 do gene TGF-β1 e PE. Fatores como histórico familiar e primiparidade foram associados com o risco de desenvolvimento de PE.

CASPASE-8 gene polymorphisms (rs13416436 and rs2037815) are not associated with preeclampsia development in Brazilian women.

BACKGROUND: Preeclampsia is responsible for considerable mortality and morbidity of mother and sibling. The etiology of preeclampsia is still unknown. Family studies indicate the involvement of genes located on chromosome 2 in preeclampsia development. Considering the importance of apoptosis and chromosome 2, one promising candidate for the study of the genetic cause of this syndrome is the CASPASE-8 gene, which was chosen as the subject of this study. OBJECTIVE: The aim of this study was to determine the frequencies of the genotypes for CASP8 gene polymorphisms (rs13416436 and rs2037815) and to associate these with preeclampsia development in Brazilian women. METHODS: Women with and without preeclampsia were investigated. Accordingly, peripheral blood was collected and DNA extracted, followed by genotyping using Real-time PCR with hydrolysis probe (Taqman® Life Technologies). RESULTS: The results showed no association between genotypes and preeclampsia development for both polymorphisms studied (χ2 = 1.03; p = 0.59, for rs13416436 and χ2 = 1.06; p = 0.58 for rs2037815). CONCLUSIONS: It seems that CASP8 gene polymorphisms (rs13416436 and rs2037815) are not important candidates for the development of preeclampsia. Other genes related to the apoptosis process or other polymorphisms in this gene should be studied in order to understand better the etiology of preeclampsia.

Profissionais de Unidades Básicas de Saúde sobre a triagem neonatal / Professionals in Basic Health Units about neonatal screening

Objetivo Descrever o conhecimento dos profissionais de saúde sobre a triagem neonatal. Métodos Trata-se de um estudo exploratório, descritivo, quantitativo realizado com 122 profissionais de saúde (57 enfermeiros, 57 técnicos de enfermagem e 8 médicos) que trabalhavam nas Unidades Básicas de Saúde de Uberaba, Minas Gerais. Os participantes responderam a um questionário semiestruturado e os dados foram analisados de forma descritiva. Resultados Houve predomínio do sexo feminino (93,5%) e idade média de 39 anos. Quanto às doenças detectadas pela triagem neonatal, a fibrose cística e anemia falciforme foram citadas por 89,4% dos participantes, a fenilcetonúria e hipotireoidismo congênito por 78,9% e 75,6%, respectivamente, e a hiperplasia adrenal congênita por 43,1%. Apenas 24,4% dos participantes mencionaram a deficiência da biotinidase. A maioria dos participantes (aproximadamente 90.0%) citaram que a triagem neonatal dever ser realizada entre o terceiro e o sétimo dias de vida do neonato e que sua finalidade é a detecção de doenças tratáveis. Quanto ao momento ideal para orientações sobre a triagem neonatal, a maioria citou o pré-natal (74,8%) seguido pela alta hospitalar e antes da coleta do exame, com valores de 43,1% cada. Cerca de 30.0% dos participantes não sabiam para onde encaminhar as amostras após a coleta e 70.0% não realizaram reciclagens sobre o assunto. Conclusão Os resultados mostram um conhecimento insuficiente sobre triagem neonatal. Essa lacuna poderia ser preenchida com ações de educação continuada, que proporcionariam uma melhora na qualidade da assistência prestada ao binômio mãe/filho.

Objective Describe health professionals' knowledge of neonatal screening. Methods This was an exploratory, descriptive, and quantitative study with 122 health professionals (57 nurses, 57 nursing technicians, and 8 physicians) who worked at the Basic Health Units of Uberaba, Minas Gerais. Participants answered a semi-structured questionnaire and the data was analyzed in a descriptive way. Results There was a predominance of females (93.5%), and the mean age was 39 years. As for the diseases detected by neonatal screening, cystic fibrosis and sickle cell anemia were mentioned by 89.4% of the participants, phenylketonuria and congenital hypothyroidism by 78.9% and 75.6%, respectively, and congenital adrenal hyperplasia by 43.1%. Only 24.4% of the participants mentioned biotinidase deficiency. The majority (roughly 90.0%) of the participants mentioned that Neonatal Screening should be performed between the 3rd and the 7th day of the newborn's life, and that its purpose is the detection of treatable diseases. Regarding the ideal timing for guidelines on neonatal screening, the majority cited prenatal care (74.8%) followed by hospital discharge, and before the collection of the exam, with values of 43.1% each. About 30.0% of participants did not know where to forward the samples after collection and 70.0% did not undergo refresher courses on the subject. Conclusion The results show an insufficient knowledge about neonatal screening. This gap could be filled with continuous education actions, which would improve the quality of care provided to the mother/child binomial.

KNOWLEDGE OF PUERPERAL MOTHERS ABOUT THE GUTHRIE TEST. / CONHECIMENTO DAS PUÉRPERAS SOBRE O TESTE DO PEZINHO.

OBJECTIVE: This study aimed to assess the knowledge of puerperal mothers about the Guthrie test. METHODS: A total of 75 mothers who sought primary care between October 2014 and February 2015 were investigated. The form was applied by the main researcher and the data was analyzed, using descriptive statistics with Microsoft Office Excel, and Statistical Package for Social Sciences (SPSS) programs. Association tests and statistical power were applied. RESULTS: Among the 75 mothers, 47 (62.7%) would have liked to receive more information about the newborn screening, especially regarding the correct sample collection period, followed by the screened morbidities. Most participants (n=55; 85.9%) took their children to be tested between the third and the seventh day of birth, as recommended by the Brazilian Health Ministry. Fifty-four women (72%) were unable to name the morbidities screened by the test in Minas Gerais, and they were also unaware that most have genetic etiology. The health professional who informed the mother about the Guthrie test was mainly the physician. This information was given prenatally to 57% of the cases, and to 43 % at the time of discharge from the hospital. The association test showed that mothers with higher education have more knowledge about the purpose and importance of the Guthrie test. The statistical power was 83.5%. CONCLUSIONS: Maternal knowledge about the Guthrie test is superficial and may reflect the health team's usual practice.

OBJETIVO: Identificar o conhecimento das puérperas sobre o teste do pezinho. MÉTODOS: Foram investigadas 75 puérperas que buscaram atendimento na atenção primária no período de outubro de 2014 a fevereiro de 2015. Um formulário foi aplicado pela pesquisadora principal e os dados resultantes foram analisados por estatística descritiva por meio dos programas Microsoft Office Excel e Statistical Package for Social Sciences (SPSS). Foi feito teste de associação e determinado o poder estatístico. RESULTADOS: Das 75 puérperas, 47 (62,7%) gostariam de receber maiores esclarecimentos sobre o teste do pezinho, com destaque para o período adequado de coleta, seguido pelas doenças triadas. A maioria das participantes (n=55; 85,9%) levou seu filho para realização do teste entre o terceiro e o sétimo dia de vida, conforme preconizado pelo Ministério da Saúde. Das puérperas, 54 (72%) não souberam citar quais são as doenças triadas pelo teste do pezinho em Minas Gerais nem sabiam que a maioria delas tem etiologia genética. O profissional de saúde que informou sobre esse teste foi um médico. Essa orientação ocorreu durante o pré-natal em 57% dos casos e, na alta hospitalar em 43%. O teste de associação mostrou que as mães com maior escolaridade possuem maior conhecimento sobre a finalidade e a importância do teste do pezinho. O poder estatístico encontrado foi de 83,5%. CONCLUSÕES: O conhecimento das puérperas sobre o teste do pezinho é superficial e pode ser reflexo da atuação da equipe de saúde.

Conhecimento das puérperas sobre o teste do pezinho / Knowledge of puerperal mothers about the guthrie test

RESUMO Objetivo: Identificar o conhecimento das puérperas sobre o teste do pezinho. Métodos: Foram investigadas 75 puérperas que buscaram atendimento na atenção primária no período de outubro de 2014 a fevereiro de 2015. Um formulário foi aplicado pela pesquisadora principal e os dados resultantes foram analisados por estatística descritiva por meio dos programas Microsoft Office Excel e Statistical Package for Social Sciences (SPSS). Foi feito teste de associação e determinado o poder estatístico. Resultados: Das 75 puérperas, 47 (62,7%) gostariam de receber maiores esclarecimentos sobre o teste do pezinho, com destaque para o período adequado de coleta, seguido pelas doenças triadas. A maioria das participantes (n=55; 85,9%) levou seu filho para realização do teste entre o terceiro e o sétimo dia de vida, conforme preconizado pelo Ministério da Saúde. Das puérperas, 54 (72%) não souberam citar quais são as doenças triadas pelo teste do pezinho em Minas Gerais nem sabiam que a maioria delas tem etiologia genética. O profissional de saúde que informou sobre esse teste foi um médico. Essa orientação ocorreu durante o pré-natal em 57% dos casos e, na alta hospitalar em 43%. O teste de associação mostrou que as mães com maior escolaridade possuem maior conhecimento sobre a finalidade e a importância do teste do pezinho. O poder estatístico encontrado foi de 83,5%. Conclusões: O conhecimento das puérperas sobre o teste do pezinho é superficial e pode ser reflexo da atuação da equipe de saúde.

ABSTRACT Objective: This study aimed to assess the knowledge of puerperal mothers about the Guthrie test. Methods: A total of 75 mothers who sought primary care between October 2014 and February 2015 were investigated. The form was applied by the main researcher and the data was analyzed, using descriptive statistics with Microsoft Office Excel, and Statistical Package for Social Sciences (SPSS) programs. Association tests and statistical power were applied. Results: Among the 75 mothers, 47 (62.7%) would have liked to receive more information about the newborn screening, especially regarding the correct sample collection period, followed by the screened morbidities. Most participants (n=55; 85.9%) took their children to be tested between the third and the seventh day of birth, as recommended by the Brazilian Health Ministry. Fifty-four women (72%) were unable to name the morbidities screened by the test in Minas Gerais, and they were also unaware that most have genetic etiology. The health professional who informed the mother about the Guthrie test was mainly the physician. This information was given prenatally to 57% of the cases, and to 43 % at the time of discharge from the hospital. The association test showed that mothers with higher education have more knowledge about the purpose and importance of the Guthrie test. The statistical power was 83.5%. Conclusions: Maternal knowledge about the Guthrie test is superficial and may reflect the health team's usual practice.

Prevalence of Y-chromosome sequences and gonadoblastoma in turner syndrome / Prevalência de sequências do Y e de gonadoblastoma em síndrome de turner

To assess the prevalence of Y-chromosome sequences and gonadoblastoma in patients with Turner syndrome (TS) using molecular techniques. Data source: A literature search was performed in Pubmed, limiting the period of time to the years 2005–2014 and using the descriptors: TS and Y sequences (n=26), and TS and Y-chromosome material (n=27). The inclusion criteria were: articles directly related to the subject and published in English or Portuguese. Articles which did not meet these criteria and review articles were excluded. After applying these criteria, 14 papers were left. Data synthesis: The main results regarding the prevalence of Y-chromosome sequences in TS were: (1) about 60% of the studies were conducted by Brazilian researchers; (2) the prevalence varied from 4.6 to 60%; (3) the most frequently investigated genes were SRY, DYZ3 and TSPY; (4) seven studies used only polymerase chain reaction, while in the remaining seven it was associated with FISH. Nine of the 14 studies reported gonadectomy and gonadoblastoma. The highest prevalence of gonadoblastoma (33%) was found in two studies. In five out of the nine papers evaluated the prevalence of gonadoblastoma was 10–25%; in two of them it was zero. Conclusions: According to these data, molecular analysis to detect Y-chromosome sequences in TS patients is indicated, regardless of their karyotype. In patients who test positive for these sequences, gonadoblastoma needs to be investigated.

Apresentar a prevalência de sequências do cromossomo Y por técnicas moleculares e de gonadoblastoma em pacientes com síndrome de Turner. Fontes de dados: Foi feita uma pesquisa bibliográfica no Pubmed, com limite de período entre 2005 e 2014, com os descritores Turner syndrome and Y sequences (n=26) e Turner syndrome and Y chromosome material (n=27). Os critérios de inclusão foram artigos que tivessem relação direta com o tema e publicados no idioma inglês ou português. Foram excluídos aqueles que não cumpriram esses critérios e eram do tipo revisão. Após aplicação desses critérios, 14 foram selecionados. Síntese dos dados: Os principais resultados quanto à prevalência de sequências do cromossomo Y em síndrome de Turner foram: 1 – cerca de 60% dos estudos foram feitos por pesquisadores brasileiros; 2 – a frequência variou de 4,6 a 60%; 3 – os genes SRY, DYZ3 e TSPY foram os mais investigados; 4 – a técnica de PCR foi empregada exclusivamente em sete estudos e nos sete restantes, associada à FISH. Nove dos 14 estudos apresentaram informações sobre gonadectomia e gonadoblastoma. Dois estudos relataram a maior prevalência para gonadoblastoma (33%). Cinco dos nove estudos referiram prevalência de 10 a 25% e em dois esse valor foi nulo. Conclusões: De acordo com os dados apresentados, é indicada a pesquisa molecular para sequências do cromossomo Y em pacientes com ST, independentemente do cariótipo. Naquelas com positividade para essas sequências, é necessária a investigação de gonadoblastoma.

[Prevalence of Y-chromosome sequences and gonadoblastoma in Turner syndrome]. / Prevalência de sequências do Y e de gonadoblastoma em síndrome de Turner.

OBJECTIVE: To assess the prevalence of Y-chromosome sequences and gonadoblastoma in patients with Turner syndrome using molecular techniques. DATA SOURCE: A literature search was performed in Pubmed, limiting the period of time to the years 2005 to 2014 and using the descriptors: Turner syndrome and Y sequences (n=26), and Turner syndrome and Y-chromosome material (n=27). The inclusion criteria were: articles directly related to the subject and published in English or Portuguese. Articles which did not meet these criteria and review articles were excluded. After applying these criteria, 14 papers were left. DATA SYNTHESIS: the main results regarding the prevalence of Y-chromosome sequences in Turner syndrome were: 1-about 60% of the studies were conducted by Brazilian researchers; 2-the prevalence varied from 4.6 to 60%; 3-the most frequently investigated genes were SRY, DYZ3 and TSPY; 4-seven studies used only PCR, while in the remaining seven it was associated with FISH. Nine of the 14 studies reported gonadectomy and gonadoblastoma. The highest prevalence of gonadoblastoma (33%) was found in two studies. In five out of the nine papers evaluated the prevalence of gonadoblastoma was 10 to 25%; in two of them it was zero. CONCLUSIONS: according to these data, molecular analysis to detect Y-chromosome sequences in TS patients is indicated, regardless of their karyotype. In patients who test positive for these sequences, gonadoblastoma needs to be investigated.

Identification of Y-Chromosome Sequences in Turner Syndrome.

OBJECTIVES: To investigate the presence of Y-chromosome sequences and determine their frequency in patients with Turner syndrome. METHODS: The study included 23 patients with Turner syndrome from Brazil, who gave written informed consent for participating in the study. Cytogenetic analyses were performed in peripheral blood lymphocytes, with 100 metaphases per patient. Genomic DNA was also extracted from peripheral blood lymphocytes, and gene sequences DYZ1, DYZ3, ZFY and SRY were amplified by Polymerase Chain Reaction. RESULTS: The cytogenetic analysis showed a 45,X karyotype in 9 patients (39.2 %) and a mosaic pattern in 14 (60.8 %). In 8.7 % (2 out of 23) of the patients, Y-chromosome sequences were found. This prevalence is very similar to those reported previously. The initial karyotype analysis of these patients did not reveal Y-chromosome material, but they were found positive for Y-specific sequences in the lymphocyte DNA analysis. CONCLUSION: The PCR technique showed that 2 (8.7 %) of the patients with Turner syndrome had Y-chromosome sequences, both presenting marker chromosomes on cytogenetic analysis.