Clinical characteristics and CYP17A1 gene mutation analysis in patients with 17α-hydroxylase/17, 20-lyase deficiency and testicular tumor / 中华内科杂志

The 17α-hydroxylase/17, 20-lyase deficiency (17-OHD) is a rare disease. The clinical characteristics and gene mutation of 2 late-diagnosed 17-OHD patients with testicular tumor admitted to our hospital from March 2018 to February 2019 were analyzed retrospectively. The two 17-OHD patients were female (46, XY). Laparoscopic abdominal exploration found undeveloped testicles in grey-yellow or grey-red in the groin and iliac fossa. The testicles were removed and showed malignancy in pathology study. Sequencing of the CYP17A1 gene identified c.1247G>A/c.1427T>C and c.985_987delTACinsAA/c.1306G>A complex heterozygous mutations. Taking together, the possibility of 17-OHD should be considered in patients with hypertension, hypokalemia, adrenal adenomatoid hyperplasia together with 46, XY gonadal dysplasia, so as to make early diagnosis and treatment, and avoid dysplastic testicular turning to malignancy.

CYP17 inhibitors improve the prognosis of metastatic castration-resistant prostate cancer patients: A meta-analysis of published trials

Background and Aims: CYP17 inhibitors can block androgen production both intratumorally and systemically, thus attenuating the progression of prostate cancer (PCa). Many randomized controlled trials (RCTs) showed promising results that men with metastatic castration-resistant PCa (mCRPC) might benefit from treatment with CYP17 inhibitors such as abiraterone acetate and orteronel. The goal of this study was to evaluate the efficacy of CYP17 inhibitors for the prognosis in patients with mCRPC. Materials and Methods: Studies were identified in PubMed/MEDLINE, the Cochrane Library, and the Web of Science. The RCTs with mCRPC patients focusing on the efficacy of CYP17 inhibitors were involved. Then, we analyzed the patients' prognosis such as overall survival (OS) and radiographic progression-free survival (RPFS). Results: A meta-analysis of the pooled data from seven randomized Phase III clinical trials was performed to compare 5516 mCRPC patients with CYP17 inhibitors versus that with placebo. Compared to placebo, the CYP17 inhibitors significantly increased the OS (pooled hazard ratios [HR]: 0.816, 95% confidence interval [CI]: 0.750–0.887), RPFS (pooled HR: 0.647, 95% CI: 0.557–0.752), and time to prostate-specific antigen (PSA) progression (pooled HR: 0.599, 95% CI: 0.517–0.693). Additional endpoints such as PSA response rate, objective response assessed by Response Evaluation Criteria in Solid Tumors, and time to initiation of chemotherapy were included in this study and were found having significant improvement with CYP17 inhibitors compared to placebo. Conclusion: This research showed that CYP17 inhibitors had a significant improvement on prognosis of patients with mCRPC within a relative safety profile both in pre- and post-chemotherapy trials. These expected results provide evidence for the use of CYP17 inhibitors to treat mCRPCs

Analysis of CYP17A1 gene variants in 5 patients with 17-hydroxylase deficiency / 中华医学遗传学杂志

Objective@#To identify pathogenic variants in 5 sporadic patients and two Chinese pedigrees affected with 17-hydroxylase deficiency (17-OHD).@*Methods@#Peripheral blood samples were collected with informed consent. Variants of CYP17A1 gene were screened by PCR and Sanger sequencing. Suspected mutations were validated in other members of the pedigrees.@*Results@#Gene sequencing has identified a homozygous c. 985_987delTACinsAA (Y329Kfs) mutation in exon 6 of the CYP17A1 gene in 4 patients and the sister of case 3. Case 1 was found to harbor compound heterozygous mutations c. 1459_1467del9 (p.D487_F489del) and c. 1244-3C>A. The parents and brother of cases 2 and 5 were heterozygous carriers of a c. 985_987delTACinsAA(Y329Kfs) mutation.@*Conclusion@#Mutations of the CYP17A1 gene probably underlie the pathogenesis of 17-OHD, for which c. 985_987delTACinsAA(Y329Kfs) is the most common. The c. 1244-3C>A is a novel mutation. Above results have facilitated genetic counseling for the affected families.

Study on six patients with 17α-hydroxylase/17, 20-lyase deficiency / 中华内分泌代谢杂志

Objective@#To improve the understanding of 17α-hydroxylase/17, 20-lyase deficiency(17OHD)disease.@*Methods@#The clinical data of six patients suffering from 17OHD were analyzed retrospectively.@*Results@#Two patients with complete combined defect had typical clinical presentations, including absence of secondary sexual characteristics, primary amenorrhea, hypertension, hypokalamia, lower gonadal hormone levels, as well as elevated corticotropin and progesterone levels. TAC329AA homozygous mutation, IVS1+ 2T>C, and c. 775_776delAT complex heterozygous mutation were found in 2 cases. Four cases of partial combined defect showed high progesterone, lower gonadal hormones and dehydroepiandrosterone-sulfate levels. Three females(46, XX)showed spontaneous menstrual and primary infertility, and two of them got successful pregnancy with assisted reproductive technology. TAC329AA heterozygous mutation was found in those 4 cases.@*Conclusions@#TAC329AA mutation is common in 17OHD, and heterozygous or homozygous mutation of TAC329AA may be the genetic and molecular basis for determining whether these patients present as partial or complete defect. The elevated plasma progesterone in non-pregnancy combined with lower gonadal hormones and dehydroepiandrosterone-sulfate is the main character of patients with partial 17OHD. Less severe patients may be able to get successful pregnancy with assisted reproductive technology.

Study on six patients with 17α-hydroxylase/17,20-lyase deficiency / 中华内分泌代谢杂志

Objective To improve the understanding of 17α-hydroxylase/17, 20-lyase deficiency ( 17OHD ) disease. Methods The clinical data of six patients suffering from 17OHD were analyzed retrospectively. Results Two patients with complete combined defect had typical clinical presentation, including absence of secondary sexual characteristics, primary amenorrhea, hypertension, hypokalamia, lower gonadal hormone levels, as well as elevated corticotropin and progesterone levels. TAC329AA homozygous mutation,IVS1+2T＞C, and c.775 776delAT complex heterozygous mutation were found in 2 cases. Four cases of partial combined defect showed high progesterone, lower gonadal hormones and dehydroepiandrosterone-sulfate levels. Three females (46, XX) showed spontaneous menstrual and primary infertility, and two of them got successful pregnancy with assisted reproductive technology. TAC329AA heterozygous mutation was found in those 4 cases. Conclusions TAC329AA mutations are common in 17OHD, and heterozygous or homozygous mutation of TAC329AA may be the genetic and molecular basis for determining whether these patients present as partial or complete defect. The elevated plasma progesterone in non-pregnancy combined with lower gonadal hormones and dehydroepiandrosterone-sulfate is the main character of patients with partial 17OHD. Less severe patients may be able to get successful pregnancy with assisted reproductive technology.

Uyhan and Han Nationality Patients with Polycystic Ovary Syndrome in Xinjiang: Polymorphism of CYP 17 Gene and Its Relationship with Pathogenesis / 现代生物医学进展

Objective:To explore the genetic polymorphism of cytochrome P450 enzyme 17(CYP17) and its relationship with the pathogenesis ofpolycystic ovary syndrome(PCOS).Methods:A total of 260 patients with PCOS of uyhan and han nationality in Xinjiang,who were admitted to Chinese Medicine Research Institute of Xinjiang Uygur Autonomous Region from January 2015 to February 2017,were chosen as PCOS group;the other 237 healthy fertile women,who were examined in the outpatient department during the same period,were chosen as control group.The CYP17 gene polymorphism in the two groups of subjects was detected by the restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) technique;the distribution of alleles and gene frequencies was compared between the two groups;combining with its clinical data,the relationship between CYP17 gene polymorphism and the pathogenesis of PCOS was analyzed.Results:Body Mass Index(BMI) and Follicle-stimulating hormone(FSH) levels in the PCOS group were lower than those in the control group;Luteotropic hormone(LH),Testosterone(TES) and LH/FSH levels in the PCOS group were higher than those in the control group,and the differences were statistically significant (P＜0.05).The frequencies of A1A1,A1A2,and A2A2 of CYP17 gene in the PCOS group were 34.62％,41.92％,23.46％,respectively,compared with 34.18％,43.88％,21.94％ in the control group,the difference was not statistically significant (P＞0.05).The allele frequency of A1 and A2 in the PCOS group were 55.58％,and 44.42％ respectively,compared with 56.12％ and 43.88％ in the control grouP,the difference was not statistically significant (P＞0.05).There was not statistical significance in FSH,LH and LH/FSH levels of different CYP17 genotypes in the PCOS group (P＞0.05).There was statistical significance in BMI level A2A2＞A1A2＞A1A1 and TES level A2A2＜A1A1＜A1A2 in the PCOS group (all P＜0.05).The BMI,FSH,LH,TES and LH/FSH levels of different CYP17 genotypes in the control group were not statistically significant (P＞0.05).Conclusion:CYP17 gene-34bp T/C nucleotide polymorphisms is a common base replacement in the population,which is not significantly related to the pathogenesis of PCOS.

Siblings with congenital adrenal cortex hyperplasia (17-α-hydroxylase deficiency) and literature review / 临床儿科杂志

Objective To report clinical characteristics and genetic results of two sisters suffered from congenital adrenal cortex hyperplasia (17-α-hydroxylase deficiency), and relevant literatures were reviewed. Methods Clinical manifestation and laboratory examination data of two sister cases of 17-α-hydroxylase deficiency enrolled in Capital Institute of Pediatrics in March 2016 were analyzed. Sanger sequencing and MLPA for CYP17A1 genes were performed and the parents' genes were also verified. Results The two patients were four years and 10 years old, both suffered from hypokalemia after infections, and hypergonadotrophin gonad hypofunction. One case was with slightly high blood pressure. Laboratory test results showed potassium fluctuation tendency in 1.9~4.0 mmol/L, 17-OHP and DHEA was decreased. Enhanced CT showed different degree of adrenal gland enlargement. Chromosome examination of the older sister is 46, XY. Both sisters demonstrated heterozygous mutation of CYP17A1 gene. The molecular genetic analysis suggested a c.985_987delTACinsAA from father and a deletion spanning exons 1-7 of the CYP17A1 gene from mother. Conclusion 17-α-hydroxylase enzyme deficiency can be diagnosed before adolescence. Clinical hypokalemia with unknown reason and high blood pressure may indicate the disease. The diagnosis can be confirmed with gene sequencing of CYP17A1.

Analysis on correlation between CYP17 gene polymorphism and hyperandrogenmia in Xinjiang Uyghur patients with polycystic ovary syndrome / 国际检验医学杂志

Objective To investigate the correlation between the CYP17 gene polymorphisms and hyperandrogenemia(HA) in Uygur women patients with polycystic ovary syndrome (PCOS ) .Methods 59 Uygur patients with PCOS were selected as the Uygur PCOS group and re-divided into the Uygur PCOS complicating HA group and Uygur PCOS non-complicating HA group . Meanwhile 18 Han patients with PCOS complicating HA were selected as the Han PCOS group .The polymerasechain reaction-restrictive fragment length polymorphism method was used to examine the basic group polymorphisms in the promoter region of CYP17 gene .Then the correlation between basic group locus polymorphism and Uygur PCOS complicating HA was analyzed .Results There was no statistically significant difference between TT ,TC and CC genotypes and T ,C allele frequencies in the Uygur PCOS non-complicating HA group and Uygur PCOS complicating HA group (P＞ 0 .05) .There was no statistically significant difference between TT ,TC and CC genotypes and T ,C allele frequencies in the Uygur PCOS complicating HA group and Han P-COS group(P＞0 .05) .The serum testosterone level in TT ,TC and CC genotypes patients of the Uygur PCOS complicating HA group was significantly higher than that in the Uygur PCOS non-complicating HA group(P＜0 .05) .Serum testosterone level had no statistically significant difference between TC ,CC genotypes and TT genotype patients of Uygur PCOS group(P＞0 .05) .Conclusion The distribution frequency of CYP17 genotypes does not increase the risk suffering from HA in Uygur women .Single nucleotide polymorphism in CYP17 gene promoter region had no obvious correlation with Uygur PCOS complicating HA occurrence .

Adrenal glands of Spix's yellow-toothed cavy (Galea spixii, Wagler, 1831): morphological and morphometric aspects / Glândulas adrenais de preás (Galea spixii, Wagler, 1831): aspectos morfológicos e morfométricos

Abstract Considering the physiological importance and need of greater morphophysiological knowledge of adrenal glands, the aims of present study were compare the morphometric data between left and right adrenal of male and female; perform a histological, scanning and transmission electron microscopy study showing tissue constitution of glands; finally, in order to define the presence and correct site of the cytochrome P450c17 expression in adrenal glands, immunohistochemical study of this enzyme was performed in 18 adrenal glands (right n=9 and left n=9) of nine adult Galea spixii (four males and five females). Right adrenal was more cranially positioned than left adrenal; dimensions (weight, length and width) of right adrenal was larger than left adrenal; no differences between male and female body and adrenal measurements were found; the morphology of cells and different amounts of lipid droplets may be related to the different demands of steroid hormones production, related to each zone of the adrenal cortex; and, the cytochrome P450c17 immunolocalization in fasciculate and reticular zone may be related with synthesis of 17-hydroxy-pregnenolone, 17-hydroxy-progesterone, dehydroepiandrosterone or androstenedione.

Resumo Considerando a importância fisiológica e a necessidade de melhor conhecimento morfofisiológico das glândulas adrenais, os objetivos do presente estudo foram comparar dados morfométricos entre adrenais direitas e esquerdas de machos e fêmeas; realizar estudos histológicos e microscopia eletrônica de varredura e transmissão revelando a constituição tecidual das glândulas; finalmente, foi realizado estudo imunohistoquímico com objetivo de definir a presença e correto sítio de expressão da citocromo P450c17 nas glândulas adrenais em 18 glândulas adrenais (direita n=9 e esquerda n=9) de nove Galea spixii adultos (quatro machos e cinco fêmeas). A glândula adrenal direita estava posicionada mais cranialmente que a adrenal esquerda; as dimensões (peso, comprimento e largura) da glândula adrenal direita foram maiores que as da esquerda; não houve diferença entre as medidas corpóreas e das adrenais entre machos e fêmeas; a morfologia das células e diferentes quantidades de gotículas lipídicas podem estar relacionadas a diferentes demandas na produção de hormônios esteroides relacionados a cada zona do córtex adrenal; e, a imunolocalização da citocromo P450 na zona fasciculada e reticular pode estar relacionado com a síntese de 17-hidroxi-pregnenolona, 17-hidroxi-progesterona, dehidroepiandrosterona ou androstenediona.

A cross-sectional study to assess any possible linkage of C/T polymorphism in CYP17A1 gene with insulin resistance in non-obese women with polycystic ovarian syndrome.

Background & objectives: Insulin resistance (IR) is a major confounding factor in polycystic ovarian syndrome (PCOS) irrespective of obesity. Its exact mechanism remains elusive till now. C/T polymorphism in the -34 promoter region of the CYP17 gene is inconsistently attributed to elucidate the mechanism of IR and its link to hyperandrogenemia in obese PCOS patients. In the present study we aimed to evaluate any association of this polymorphism with IR in non-obese women with PCOS. Methods: Polymorphism study was performed by restriction fragment length polymorphism (RFLP) analysis of the Msp A1 digest of the PCR product of the target gene in 75 PCOS cases against 73 age and BMI matched control women. Serum testosterone, BMI and HOMA-IR (homeostatic model of assessment-insulin resistance) were analyzed by standard techniques. A realistic cut-off value for the HOMA-IR was obtained through receiver operating characteristic (ROC) curve for exploring any possible link between IR and T/C polymorphism in the case group. Results: Significant increases in serum testosterone and HOMA-IR values were observed among the case group (P<0.001) without any significant elevation in BMI and FBG compared to controls. Cut-off value for IR in the PCOS patients was 1.40 against a maximum sensitivity of 0.83 and a minimum false positivity of 0.13. The analysis revealed an inconclusive link between the C/T polymorphic distribution and insulin resistant case subjects. Interpretation & conclusions: The results showed that CYP17A1 gene was not conclusively linked to either IR or its associated increased androgen secretion in non-obese women with PCOS. We propose that an increased sensitivity of insulin on the ovarian cells may be the predominant reason for the clinical effects and symptoms of androgen excess observed in non-obese PCOS patients in our region.

CYP17, CYP19, and NQO1 Genetic Polymorphisms and Breast Cancer Susceptibility in Young Women in Brazil.

Aims: Breast cancer is the most common cancer in women worldwide, being exposure to estrogens the acknowledged main risk factor. CYP17, CYP19 and NQO1 are enzymes involved in the estrogen metabolism, so their polymorphisms may be involved in breast carcinogenesis. The aim of this study was to determine the magnitude of the association between CYP17 MspA1, CYP19 Arg264Cys, and NQO1 C609T polymorphisms and breast cancer in young women. Methods: This is a hospital-based case-control study carried out in Rio de Janeiro. Cases were 270 women with age range 18-35 years and a histopathological diagnosis of breast cancer between 1999-2009. Controls were 270 women without cancer at the same age range. Results: An association between CYP17 MspA1 or CYP19 Arg264Cys polymorphisms and breast cancer were not observed (OR = 1.02, 95% CI 0.72-1.44 for CYP17 genotypes TC/CC and OR = 0.85, 95% CI 0.48-1.49 for CYP19 genotypes CT/TT). However, a statistically significant increased risk estimate was identified in women who had at least one NQO1 polymorphic allele (T), OR= 1.96, 95% CI 1.13-3.40 following adjustment for selected confounders. Conclusion: This study suggests that the NQO1 609T polymorphism may be a risk factor for breast carcinogenesis in women less than 36 years in Brazil.

Approach to the patient with 17α-hydroxylase/17, 20-lyase deficiency / 中华内分泌代谢杂志

17α-hydroxylase/17,20-lyase deficiency (17OHD) is a rare cause of congenital adrenal hyperplasia.The patient predominantly presents with low-renin hypertension,hypokalemia,lack of secondary sexual development,and in women with primary amenorrhea,in male with pseudohermaphroditism.We herewith analyse the clinical features of a case of 17OHD diagnosed by gene sequencing.And the etiology,clinical manifestations,genetic features,diagnosis and treatment for 17OHD were reviewed.

An unique exonic splicing mutation in the CYPI7AI gene as the cause of steroid 17α-hydroxylase deficiency / 中华内分泌代谢杂志

Objective To analyze CYP17A1 gene mutation in a patient with 46,XY disordered sex development and to explore the possible influence on the phenotype of the patient.Methods Eight exons of CYP17AI gene in the patient and her parents were amplified and directly sequenced.In order to construct Mini-gene system,PCR fragments containing wildtype and mutant splicing sites were inserted in expression vector,and then transfected into cells.RT-PCR was used to observe the influence of splicing site mutation.Wildtype and aberrant splicing CYP17A1 cDNA expression plasmids were constructed and transfected into cells respectively,and CYP17A1 enzyme activity was tested in vitro.Results Mutation analysis revealed compound heterozygous CYP17A1 mutations,with Y329fs in one allele and a synonymous substitution( c.1263G＞A:GCG＞GCA) in another allele.In vitro analysis showed that the synonymous substitution induced a novel splicing site,which resulted in aberrant splicing of CYP17A1 mRNA and lacked six or seven amino acids after 415 in splicing product.In vitro transfection and enzyme activity experiment showed that the aberrant splicing product abolished the enzyme activity completely.However,this mutation did not completely influence splicing.The patient also had a part of normal splicing product,which was a coincidence to the phenotype of the patient.Conclusion This is the first description of an exonic splicing mutation in CYP17A1 relevant to the 17ot-hydroxylase deficiency phenotype.The functional study of the aberrant splicing variant has been initiated.

Distinctive profile of the 17-hydroxylase and 17,20-lyase activities revealed by urinary steroid metabolomes of patients with CYP17 deficiency / Perfil característico das atividades 17-hidroxilase e 17,20-liase reveladas por meio do metaboloma de esteroides urinários de pacientes com deficiência de CYP17

OBJECTIVES: (1) Characterize serum (S) and urinary (U) steroid metabolites in complete CYP17 deficiency (cCYP17D); (2) analyze the relative 17α-hydroxylase (17OH) and 17,20-lyase (17,20L) activities in vivo; and (3) comparedata from the two most prevalent mutations in Brazil. SUBJECTS AND METHODS: 20 genotyped cCYP17D patients from a previously reported cohort were homozygous for W406R or R362C; 11 controls were CYP17 wild types (WT). WT and cCYP17D patients had S and U samples drawn to measure: cortisol (F), corticosterone (B), deoxycorticosterone (DOC), 18OH-B, 18OH-DOC, and 17OHP; and tetrahydro (TH)-B, THA, THDOC, THF+5α-THF, TH-cortisone, androsterone, etiocholanolone, 5-pregnenediol, 17OH-pregnenolone and pregnanetriol. RESULTS: Compared to WT, cCYP17D patients had marked elevations of B, DOC, 18OH-B and 18OH-DOC, whereas 17OHP, F and adrenal androgens (AA) were reduced; U steroids parallel S findings. Metabolite ratios revealed that both 17OH and 17,20L activities were impaired in cCYP17D. There were nodifferences between W406R andR362C mutations. CONCLUSIONS: cCYP17D patients show parallel overproduction/overexcretion of 17-deoxysteroids, and marked reduction of F and AA. In addition to 17OH, 17,20-L activity was also impaired in cCYP17D. W406 and R362C mutations disclose similar Sand U patterns.

OBJETIVOS: (1) Caracterizar os esteroides séricos (S) e urinários (U) na deficiência completa da CYP17 (DcCYP17); (2) analisar as atividades da 17α-hidroxilase (17OH) e 17,20-liase (17, 20 L) in vivo; e (3) comparar as duas mutações mais prevalentes no Brasil. SUJEITOS E MÉTODOS: 20 pacientes genotipados para a DcCYP17, de uma coorte anterior, eram homozigotos para W406R ou R362C (8 cada); 11 controles eram CYP17 wild types (WT). Amostras de S e U foram colhidas dos WT e pacientes para dosagem de: cortisol (F), corticosterona (B), deoxicorticosterona (DOC), 18-OH-B, 18OH-DOC e 17OHP; e tetraidro(TH)-B, THA, TH-DOC, THF+5α-THF, THE, androsterona, etiocolanolona, 5-pregnenediol, 17OH-pregnenolona e pregnanetriol. RESULTADOS: Comparados aos WT, os pacientes com DcCYP17 revelaram elevações acentuadas de B, DOC, 18OHB e 18OHDOC, enquanto 17OHP, F e andrógenos adrenais (AA) estavam reduzidos. Os esteroides na U acompanham os achados no S. As relações de metabólitos mostraram que as atividades de 17OH e 17,20L estavam reduzidas em pacientes com DcCYP17. Não houve diferenças entre pacientes com as mutações W406R e R362C. CONCLUSÕES: Na DcCYP17, a produção e a excreção dos 17-deoxiesteroides estão aumentadas em paralelo, em contraste com a reduzida produção/excreção de F e AA. As atividades da 17OH e 17,20-L estão diminuídas na DcCYP17. As mutações W406 e R362C apresentam achados semelhantes em S e U.

Identification of steroid biosynthetic defects in genotype-proven heterozygote individuals with 17α-hydroxylase/17,20-lyase deficiency / 中华内分泌代谢杂志

Objective To investigate the adrenal steroidogenic function in genotype-proven heterozygotes carrying mutations in CYP17A1 gene in vivo. Methods Eight patients and 14 family members from 5 families with 17-hydroxylase/17,20-lyase deficiency (17OHD) were recruited. The mutations of the CYP17A1 gene in these individuals were screened by direct sequencing of PCR products. The hormonal response to ACTH was evaluated in the 14 genotype-proven carriers and 45 age- and sex-matched normal subjects. Results Three mutations were found in 5 unrelated families. 14 carriers with CYP17A1 mutation were identified, including 7 heterozygotes with D487_F489del, 6 with Y329fs, and 1 for H373L. Compared to the normal subjects, the carriers exhibited lower basal and ACTH-stimulated cortisol levels, but higher ACTH-stimulated corticosterone level. The ratios of corticosterone to cortisol in the genotype-proven heterozygotes were higher than those of normal individuals at baseline and following ACTH-stimulation. Similarly, progesterone level and ratios of progesterone to 17-hydroxyprogesterone in the male heterozygotes were also higher than that of normal individuals before and after stimulation. No significant differences were observed in the hormone levels between two genotypes (D487_F489del vs Y329fs). Conclusions Genotype-proven carriers of 17OHD without apparent clinical symptoms exhibit decreased enzyme activity,analogous to mildly impaired adrenal 21-hydroxylase activity in the carriers of CYP21 A2 gene mutation.

Relación entre el polimorfismo -34 Bp de la región promotora del gen CYP17 con el perfil hormonal y metabólico en mujeres con diabetes mellitus tipo 1 / Relationship of -34 Bp polymorphism in the promoter of Cyp17 gene with hormonal and metabolic profile in women with type 1 diabetes mellitus

The P450c17a enzyme has a central role in ovarian hyperandrogenism, which is a characteristic of polycystic ovary syndrome (PCOS). Several studies have suggested a possible role for the CYP17 gene, which codes for the enzyme P450c17a and the -34bp T-C polymorphism in the development of hyperandrogenism. The presence of the cytosine, know as A2 allele, has been associated with hyperandrogenism in patients with PCOS. Objective: To evaluate the frequency and association of the -34bp polymorphism in the CYP17 gene and determine its association with hormonal and metabolic characteristics in women with DM1. Patients and Methods: The CYP17 polymorphism was studied in 72 DM1 and 71 control women by PCR and RFLP analysis. The CYP17 genetic dosage was compared with the antropometrical characteristics and the serum concentrations of testosterone, androstenedione, DHEAS and 17OH progesterone in women with DM1. Results: Genotype A2/A2 was present in 20.8 percent and 7.1 percent of DM1 and controls, respectively (p = 0,034). Allele A2 was present in 40.3 percent and 27.5 percent of DM1 and healthy women, respectively (p = 0,031). No association between CYP17 genotypes and hormonal or metabolic characteristics was observed. Conclusion: This study shows that the frequency of the A2/A2 genotype was higher in women with DM1 than in the control group. However, no association between the presence of the polymorphism and circulating steroid levels or BMI was observed.

Clinical and Genetic Analysis for 10 Patients with 17? Hydroxylase/17, 20 Lyase Deficiency / 上海第二医科大学学报

Objective To analyze the clinical and genetic characteristics of 10 Chinese patients with 17? hydroxylase/17,20 lyase deficiency (17OHD). Methods Clinical features and laboratory data were collected from 7 kindreds with 17OHD. PCR products and subclone sequencing were performed to screen the mutation of CYP17A1 gene. Results All patients had typical clinical presentation of sexual infantilism, hypertension and hypokalemia. The laboratory examinations indicated decreased plasma cortisol, 17-hydroxy progesterone, estradiol and testosterone, and elevated blood adrenocorticotrophic hormone(ACTH), follcie-stimulating hormone(FSH) and luteinizing hormone(LH). CT scan showed bilateral adrenal hyperplasia. 5 CYP17A1 mutations were identified, 4 of which are novel types D487_F489del, the most frequent mutation, was identified in 4 families and 45% alleles. Conclusion Our study indicates that 17OHD should be considered in the diagnosis of patients with sexual infantilism. D487_F489del is the most frequent mutation in Chinese 17OHD patients.

Association of the CYP17 gene polymorphism with the risk of advanced endometriosis in Korean women / 대한산부인과학회지

OBJECTIVE: To investigate whether polymorphism of CYP17 gene is associated with the risk of advanced endometriosis in Korean women. METHODS: The 194 endometriosis patients and 209 controls were enrolled. Blood samples were collected from 194 patients with endometriosis stages III and IV diagnosed by both pathologic and laparoscopic findings. The women undergoing laparoscopic surgery or laparotomy for non-malignant lesions were included in the control group. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) of PCR products were done to determine all individuals' genotype. RESULTS: The heterozygous allele in CYP17 gene was most common genotypes in both endometriosis and healthy control groups (54.6% vs. 38.8%). In women with heterozygous A1/A2 genotype, there was increased endometriosis risk and this difference was statistically significant (p<0.05). CONCLUSION: The results suggest that the CYP17 genetic polymorphism might be associated with advanced endometriosis risk in Korean women.

Association of the CYP17 gene polymorphism with the risk of PCOS in Korean women / 대한산부인과학회지

OBJECTIVE: To investigate whether polymorphism of CYP17 gene is associated with the risk of polycystic ovary syndrome (PCOS) in Korean women. METHODS: The 86 PCOS patients and 75 controls were enrolled. Blood samples were collected from 86 patients diagnosed according to the 2003 revised criteria of the Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group. Age matched women with regular menstruation from same geographic region were recruited on the control subject. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) of PCR products were done to determine all individuals' genotype. RESULTS: In women with A1A1 genotype, there was increased PCOS risk and this difference was statistically significant (OR 2.2 (CI 1-4.7)). CONCLUSION: The results suggest that the CYP17 A1A1 genetic polymorphism might be associated with PCOS risk in Korean women.

Combined deficiency of steroid 17-?-hydroxylase/17 and 20-lyase induced by mutation of homozygous 985del TAC insAA of CYP17 gene / 解放军医学杂志

Objective To analyze the CYP17 gene of two sisters with combined 17-alpha-hydroxylase/17, 20-lyase deficiency, and that of their parents. Methods Genomic DNA of the four members was prepared from peripheral blood by standard methods. All the eight exons and intron/exon boundaries of CYP17 were PCR amplified and sequenced. All the hormone levels were measured by time-resolved immunofluorometric assay. Results Combined 17-?-hydroxylase/17, 20-lyase deficiency was confirmed by marked hormone change. Sequence analysis revealed that the sisters were homozygous 985delTACinsAA of CYP17, and their parents were heterozygous 985delTACinsAA. Conclusion Novel mutation of 985delTACinsAA in CYP17 was found in two sisters with 17-?-hydroxylase/17, 20-lyase deficiency. The homozygous one can induced the phenotype and the heterozygous one is a genomic marker.