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Journal ArticleDOI: 10.1080/09513590.2020.1770724

CYP17 gene polymorphic sequence variation is associated with hyperandrogenism in Kashmiri women with polycystic ovarian syndrome.

04 Mar 2021-Gynecological Endocrinology (Taylor & Francis)-Vol. 37, Iss: 3, pp 230-234
Abstract: Polycystic ovarian syndrome is a complex reproductive as well as endocrinological disorder characterized by anovulatory dysfunction, androgen excess and polycystic ovarian morphology. Hyperandrogen...

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Topics: Hyperandrogenism (60%), Androgen Excess (54%)
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5 results found


Open accessJournal ArticleDOI: 10.1016/J.RBMO.2021.06.012
Xiqiao Xu1, Kaiyue Hu1, Hao Shi1, Yiping Yu1  +2 moreInstitutions (1)
Abstract: Polycystic ovary syndrome (PCOS) is a multifactorial reproductive and endocrine disease, believed to be caused by aberrant steroid biosynthesis pathways involving cytochrome P450, 17α-hydroxylase (CYP17A1). This meta-analysis aimed to evaluate the association between CYP17A1 polymorphism rs743572 and PCOS risk. Studies on the CYP17A1 gene were retrieved by searching PubMed, Embase and Web of Science and statistical analyses were performed by STATA software. Fifteen eligible studies were included, dated from January 1994 to 19 November 2020, involving 2277 patients with PCOS and 1913 control individuals. Overall, the results showed that the rs743572 T>C mutation was most likely to be associated with PCOS risk under the recessive model, which was further confirmed by heterogeneity analysis and publication bias detection (CC versus CT + TT, odds ratio [OR] 1.24, 95% confidence interval [CI] 1.02–1.50, P = 0.028, I² = 35.9%). Moreover, subgroup analysis by ethnicity demonstrated that Caucasian but not Asian women carrying the CC genotype of rs743572 had an elevated risk of PCOS (CC versus CT + TT, OR 1.45, 95% CI 1.03–2.06, P = 0.035, I² = 15.10%, six studies). In conclusion, rs743572 is highly likely to be a risk factor for PCOS, and the mutant genotype CC may increase susceptibility to PCOS in Caucasians rather than Asians.

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Topics: Polycystic ovary (59%), Steroid biosynthesis (54%), Risk factor (51%) ... show more

1 Citations


Journal ArticleDOI: 10.1007/S43032-021-00700-5
Zhaojuan Chen, Lan Liu1, Xia Xi2, Martina S. Burn3  +2 moreInstitutions (4)
Abstract: As one of the most common endocrine disorders affecting women, polycystic ovary syndrome (PCOS) is associated with serious conditions including anovulation, endometrial cancer, infertility, hyperandrogenemia, and an increased risk for obesity and metabolic derangements. One contributing etiology to the pathophysiology of hyperandrogenemia associated with PCOS is an intrinsic alteration in ovarian steroidogenesis, leading to enhanced synthesis of androgens including testosterone. Studies have suggested that the increased testosterone synthesis seen in PCOS is driven in part by increased activity of CYP17A1, the rate-limiting enzyme for the formation of androgens in the gonads and adrenal cortex, which represents a critical factor driving enhanced testosterone secretion in PCOS. In this work, we evaluated the hypothesis that dysregulation of the noncoding RNA H19 results in aberrant CYP17 and testosterone production. To achieve this, we measured Cyp17 in ovarian tissues of H19 knockout mice, and quantified serum testosterone levels, in comparison with wild-type controls. We also evaluated circulating and ovarian H19 expression and correlated results with the presence or absence of PCOS in a group of women undergoing evaluation and treatment for infertility. We found that the loss of H19 in a mouse model results in decreased ovarian Cyp17, along with decreased serum testosterone in female mice. Moreover, utilizing serum samples and cumulus cells from women with PCOS, we showed that circulating and ovarian levels of H19 are increased in women with PCOS compared to controls. Findings from our multimodal experimental strategy, involving both a mouse model of dysregulated H19 expression and clinical serum and ovarian cellular samples from women with PCOS, suggest that the loss of H19 may disrupt androgen production via a Cyp17-mediated mechanism. Conversely, excess H19 may play a role in the pathogenesis of PCOS-associated hyperandrogenemia.

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Topics: Polycystic ovary (57%), Anovulation (56%), Androgen (53%) ... show more

Open accessJournal ArticleDOI: 10.1016/J.MGENE.2021.100996
R.M. Ali1, T. P. Shkurat1, A. A. Alexandrova1, E.S. Bugrimova  +2 moreInstitutions (1)
01 Feb 2022-Meta Gene
Abstract: Introduction Polycystic ovary syndrome (PCOS) affects 4–20% of women of reproductive age. The contribution of genetic factors to the etiology of PCOS is 79%, and the contribution of the environment, lifestyle and individual history is 21%. It is believed that the increased production of androgens in PCOS is a consequence of dysregulation of various genes involved in the synthesis of steroid hormones, such as CYP11, CYP17 and CYP19. Conflicting data on the association of the CYP17 gene polymorphism (rs743572) with PCOS determined the purpose of this meta-analysis - to study this association in a larger general population in order to determine whether polymorphism in the CYP17 T/C promoter is associated with an increased risk of PCOS. Methods A systematic search was carried out in various databases for articles on the relationship between rs743572 polymorphism of gene CYP17 and PCOS risk published up to May 2021. The articles were analyzed in accordance with the recommendations for systematic reviews and meta-analyzes (PRISMA). The criteria for inclusion of studies in the meta-analysis were: (i) case-control studies with healthy populations as controls; (ii) a study describing the diagnostic criteria for PCOS, sources of cases and controls; (iii) studies of genetic associations showing the frequency of genotypes of the studied polymorphism and PCOS in humans; (iv) sufficient genotype data to calculate odds ratio (OR) and 95% confidence interval (CI). The control HWE was first assessed for each study using the chi-square test (χ2). Meta-analysis was performed using Review Manager version 5.4. Odds ratios (OR) with a 95% confidence interval (CI) were used to assess the strength of the association between the rs743572 polymorphism of gene CYP17 and PCOS. Pooled OR was calculated for dominant (CC + TC vs. TT), recessive (CC vs. TC + TT), and allelic (C vs. T) models, as well as for homozygous (CC vs. TT) and heterozygous (TC vs. TT) models. Results Out of 577 potentially relevant articles, 17 articles were selected for eligibility assessment after excluding irrelevant and duplicate articles. 2283 cases and 2200 controls were evaluated to identify the relationship between the rs743572 polymorphism of the CYP17 gene and PCOS. Carriage of allele C was considered to increase the risk of PCOS. A significant association with PCOS risk was found for rs743572 in the general population using dominant, allelic and heterozygous models: (p = 0.005, OR = 1.41, 95% CI 1.11–1.79; p = 0, 006, OR = 1.28, 95% CI 1.07–1.53; p = 0.01, OR = 1.38, 95% CI 1.07–1.77), respectively. An association between this polymorphism and PCOS risk was not found in the recessive and homozygous models: (p = 0.16, OR = 1.21, 95% CI 0.93–1.58; p = 0, 08, OR = 1.31, 95% CI 0.96–1.78), respectively. Subgroup analysis according to the ethnicity of the participants showed significant associations between Asian and European populations: a higher association was found among Asian populations in the dominant model (p = 0.04, OR = 1.59, 95% CI 1.02–2.48). Conclusions The meta-analysis showed an increased risk of PCOS in carriers of the C allele rs743572, thus, polymorphism rs743572 is a risk factor for PCOS, especially in the Asian population. To determine the genetic risks of PCOS, further research is needed on different haplotypes and their association with PCOS risk.

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Topics: Polycystic ovary (54%), Gene polymorphism (52%), Population (52%) ... show more

Open accessJournal ArticleDOI: 10.5114/PM.2020.101948
Abstract: Introduction Screening of polycystic ovary syndrome (PCOS) women for hypothyroidism and hyperprolactinemia was suggested, because the undiagnosed hypothyroidism and hyperprolactinemia can aggravate the PCOS symptoms. Aim of the study To determine whether the insulin resistance (IR), hypothyroidism, and hyperprolactinemia are common endocrine disorders associated with the PCOS. Material and methods One hundred and twenty PCOS women were compared to 120 non-PCOS controls in this study. Participants' day 2-3 hormonal profile and insulin resistance (IR) using the fasting glucose and fasting insulin were evaluated. Collected data were analyzed to determine whether the IR, hypothyroidism, and hyperprolactinemia are common endocrine disorders associated with the PCOS. Results TSH and prolactin were significantly high in PCOS women (6.4 ±4.2 and 934 ±102.3, respectively) than controls (3.5 ±3.3 and 445 ±77.5 mIU/ml, respectively) (p = 0.004 and 0.001, respectively). The PCOS women had significantly high relative risk of IR (RR 3.0 (95% CI: 1.9-4.7) p < 0.0001), hypothyroidism (RR 3.4; 95% CI: 1.7-6.9) (p = 0.0005), and hyperprolactinaemia (RR 3.15; 95% CI: 1.8-5.6) (p = 0.0001) than controls. The PCOS women had higher odds of IR (OR 4.8; 95% CI: 2.6-8.8) (p < 0.0001), hypothyroidism (OR 4.29; 95% CI: 1.9-9.4) (p = 0.0003), and hyperprolactinaemia (OR 4.27; 95% CI: 2.1-8.5) (p < 0.0001) than controls. Conclusions TSH and prolactin were significantly high in studied PCOS women, and 47.5% of the studied PCOS women had IR. The PCOS women had significantly higher odds and relative risks of IR, hypothyroidism, and hyperprolactinemia than controls. IR, hypothyroidism, and hyperprolactinemia are common endocrine disorders associated with PCOS.

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Open accessJournal ArticleDOI: 10.1007/S12020-021-02894-9
05 Oct 2021-Endocrine
Abstract: Polycystic ovary syndrome (PCOS) is one of the most common reproductive, endocrine, and metabolic disorder in premenopausal women. Even though the pathophysiology of PCOS is complex and obscure, the disorder is prominently considered as the syndrome of hyperandrogenism. C-Terminal binding protein 1 antisense (CTBP1-AS) acts as a novel androgen receptor regulating long noncoding RNA (lncRNA). Therefore, the present study was aimed to establish the possible association of androgen receptor regulating long noncoding RNA CTBP1-AS with PCOS. A total of 178 subjects including 105 PCOS cases and 73 age-matched healthy controls were recruited for the study. The anthropometric, hormonal, and biochemical parameters of all subjects were analyzed. Total RNA was isolated from peripheral venous blood and expression analysis was done by quantitative real-time PCR. The correlation analysis was performed to evaluate the association between and various clinical parameters and lncRNA CTBP1-AS expression. The mean expression level of CTBP1-AS was found to be significantly higher in the PCOS women than in the healthy controls (-lnCTBP1-AS, 4.23 ± 1.68 versus 1.24 ± 0.29, P < 0.001). Furthermore, subjects with higher expression level of CTBP1-AS had significantly higher risk of PCOS compared to subjects with low levels of CTBP1-AS expression (actual OR = 11.36, 95% CI = 5.59–23.08, P < 0.001). The area under receiver operator characteristic (ROC) curve was 0.987 (SE 0.006, 95% CI 0.976–0.99). However, lncRNA CTBP1-AS was found to have no association with different clinical characteristics of PCOS. In conclusion, androgen receptor coregulating lncRNA CTBP1-AS is associated with PCOS women and high expression of CTBP1-AS is a risk factor for PCOS in Kashmiri women

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Topics: Polycystic ovary (57%), Androgen receptor (53%), Hyperandrogenism (52%)
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25 results found


Open accessJournal ArticleDOI: 10.1210/JC.2003-031122
Abstract: The objective of the present study was to estimate the prevalence of the different pathological conditions causing clinically evident androgen excess and to document the degree of long-term success of suppressive and/or antiandrogen hormonal therapy in a large consecutive population of patients. All patients presenting for evaluation of symptoms potentially related to androgen excess between October 1987 and June 2002 were evaluated, and the data were maintained prospectively in a computerized database. For the assessment of therapeutic response, a retrospective review of the medical chart was performed, after the exclusion of those patients seeking fertility therapy only, or with inadequate follow-up or poor compliance. A total of 1281 consecutive patients were seen during the study period. Excluded from analysis were 408 patients in whom we were unable to evaluate hormonal status, determine ovulatory status, or find any evidence of androgen excess. In the remaining population of 873 patients, the unbiased prevalence of androgen-secreting neoplasms was 0.2%, 21-hydroxylase-deficient classic adrenal hyperplasia (CAH) was 0.6%, 21-hydroxylase-deficient nonclassic adrenal hyperplasia (NCAH) was 1.6%, hyperandrogenic insulin-resistant acanthosis nigricans (HAIRAN) syndrome was 3.1%, idiopathic hirsutism was 4.7%, and polycystic ovary syndrome (PCOS) was 82.0%. Fifty-nine (6.75%) patients had elevated androgen levels and hirsutism but normal ovulation. A total of 257 patients were included in the assessment of the response to hormonal therapy. The mean duration of follow-up was 33.5 months (range, 6-155). Hirsutism improved in 86%, menstrual dysfunction in 80%, acne in 81%, and hair loss in 33% of patients. The major side effects noted were irregular vaginal bleeding (16.1%), nausea (13.0%), and headaches (12.6%); only 36.6% of patients never complained of side effects. In this large study of consecutive patients presenting with clinically evident androgen excess, specific identifiable disorders (NCAH, CAH, HAIRAN syndrome, and androgen-secreting neoplasms) were observed in approximately 7% of subjects, whereas functional androgen excess, principally PCOS, was observed in the remainder. Hirsutism, menstrual dysfunction, or acne, but not alopecia, improved in the majority of patients treated with a combination suppressive therapy; although more than 60% experienced side effects.

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Topics: Androgen Excess (58%), hirsutism (57%), Antiandrogen (55%) ... show more

962 Citations


Journal ArticleDOI: 10.1093/HMG/3.10.1873
A. H. Carey1, Dawn Waterworth1, Kirty Patel1, Davinia White1  +4 moreInstitutions (1)
Abstract: Fourteen Caucasian families with 81 affected individuals have been assessed in which polycystic ovaries/male pattern baldness (PCO/MPB) segregates as an autosomal dominant phenotype (1). The gene CYP17, coding for P450c17 alpha (17 alpha-hydroxylase; 17/20 lyase) on chromosome 10q24.3 is the rate-limiting step in androgen biosynthesis. We have identified a new single base change in the 5' promoter region of CYP17 by heteroduplex analysis. This creates an additional SP1-type (CCACC box) promoter site, which may cause increased expression. This base change also creates a recognition site for the restriction enzyme MspA1 allowing a simple screening procedure. There is a significant association between the presence of this base change (A2) and the affected state for consecutively identified Caucasian women with PCO as compared either to consecutively matched controls (P = 0.03) with an odds ratio for those with at least one A2 allele of 3.57, or to a random population (P = 0.02) with an odds ratio of 2.50. Within the fourteen families, members with PCO or MPB have a significant association with the occurrence of at least one A2 allele compared to their normal relatives, with an odds ratio of 2.20 (P = 0.05). The base change does not cosegregate with the affected phenotype within the families showing association, demonstrating that this mutation of CYP17 does not cause PCO/MPB. Variation in the A2 allele of the CYP17 gene is a significant factor modifying the expression of PCO/MPB in families where it has been demonstrated to segregate as a single gene disorder, but it is excluded as the primary genetic defect.

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Topics: Male-pattern baldness (58%), Polycystic ovary (54%), Allele (52%) ... show more

449 Citations


Open accessJournal Article
15 Jun 1999-Cancer Research
Abstract: The ability of a motif of the CYP17 5' untranslated region, created by a polymorphic T to C substitution, to bind to the human transcription factor Sp-1 was investigated. No binding of any of the polymorphic alleles was observed in electromobility shift assay. No other sequence within +1 to +100 of each of the CYP17 alleles formed complex with the Sp-1 or enhanced binding to the polymorphic CACC box. Genotyping of 510 breast cancer patients and 201 controls revealed no difference in genotype frequencies. Age at onset, tumor grade, lymph node status and distant metastases, stage, and estrogen and progesterone receptor status were not associated with the CYP17 genotype.

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Topics: Genotype (57%), Genotype frequency (55%), Genotyping (53%) ... show more

160 Citations


Open accessJournal ArticleDOI: 10.5152/JTGGA.2015.15232
Zeynep Ozcan Dag1, Berna DilbazInstitutions (1)
Abstract: The prevalence of obesity and overweight are increasing and have become an epidemic worldwide. Obesity has detrimental influences on all systems, including reproductive health. The prevalence of obesity in infertile women is high, and it is well known that there is an association between obesity and infertility. The relationship between obesity and reproductive functions is still being explored. Overweight women have a higher incidence of menstrual dysfunction and anovulation. Overweight and obese women are at a high risk for reproductive health. The risk of subfecundity and infertility, conception rates, miscarriage rates, and pregnancy complications are increased in these women. They have poor reproductive outcomes in natural as well as assisted conception. These poor reproductive outcomes include assisted reproduction such as ovulation induction, in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), and ovum donation cycles. Weight loss has beneficial effects on the reproductive outcomes in these patients.

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Topics: Assisted reproductive technology (64%), Infertility (61%), Overweight (58%) ... show more

134 Citations


Open accessJournal ArticleDOI: 10.3390/IJERPH15112589
Abstract: Polycystic ovarian syndrome (PCOS) is thought to be the most common endocrine disorder found in women. Common symptoms include irregular menstrual cycle, polycystic ovaries, and hirsutism, as well as an increased risk for a multitude of conditions, including insulin resistance, dyslipidemia and infertility. The prevalence of polycystic ovarian syndrome is generally thought to be between 3% and 10% but it is widely unknown for specific subpopulations based on geographical location and race/ethnicity. Based on the high degree of variability and inconsistencies between the different diagnostic criteria, there is a unique challenge that exists when determining the prevalence of this syndrome. There are a large percentage of individuals that remain undiagnosed even after visiting multiple health care providers. Most studies conducted across the world are limited by small sample size, selection bias, and lack of comparability across studies. There have been very few studies that have examined the prevalence of polycystic ovary syndrome across the United States. Based on the National Institutes of Health (NIH)’s diagnostic criteria, there is a similar prevalence of PCOS documented across the United States, the United Kingdom, Spain, Greece, Australia, and Mexico. Other studies have shown some differences between geographical location and race. The existing data is not conclusive enough to determine whether or not there is any significant differences in the prevalence of PCOS across geographical location, racial or ethnic groups. This review will seek to determine the prevalence of polycystic ovarian syndrome based on geographical location and race/ethnicity.

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Topics: Polycystic ovary (68%)

115 Citations


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