Impact of rs2414096 polymorphism of CYP19 gene on susceptibility of polycystic ovary syndrome and hyperandrogenism in Kashmiri women.
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SUBMITTER: Ashraf S
PROVIDER: S-EPMC8217560 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Several studies have reported the association of the SNP rs2414096 in the CYP19 gene with hyperandrogenism, which is one of the clinical manifestations of polycystic ovary syndrome (PCOS). These studies suggest that SNP rs2414096 may be involved in the etiopathogenisis of PCOS. To investigate whetherthe CYP19 gene SNP rs2414096 polymorphism is associated with the susceptibility to PCOS, we designed a case-controlled association study including 684 individuals.A case-controlled association study including 684 individuals (386 PCOS patients and 298 controls) was performed to assess the association of SNP rs2414096 with PCOS. Genotyping of SNP rs2414096 was conducted by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method that was performed on genomic DNA isolated from blood leucocytes. Results were analyzed in respect to clinical test results.The genotypic distributions of rs2414096 (GG, AG, AA) in the CYP19 gene (GG, AG, AA) in women with PCOS (0.363, 0.474, 0.163, respectively) were significantly different from that in controls (0.242, 0.500, 0.258, respectively) (P = 0.001). E2/T was different between the AA and GG genotypes. Age at menarche (AAM) and FSH were also significantly different among the GG, AG, and AA genotypes in women with PCOS (P = 0.0391 and 0.0118, respectively). No differences were observed in body mass index (BMI) and other serum hormone concentrations among the three genotypes, either in the PCOS patients or controls.Our data suggest that SNP rs2414096 in the CYP19 gene is associated with susceptibility to PCOS.
| S-EPMC2803167 | biostudies-literature
Project description:Context:A majority of women with polycystic ovary syndrome (PCOS) have metabolic abnormalities that result in an increased risk of developing type 2 diabetes and heart disease. Correlative studies have shown an association between changes in the gut microbiome and metabolic disorders. Two recent studies reported a decrease in ? diversity of the gut microbiome in women with PCOS compared with healthy women. Objective:We investigated whether changes in the gut microbiome correlated with specific clinical parameters in women with PCOS compared with healthy women. We also investigated whether there were changes in the gut microbiome in women with polycystic ovarian morphology (PCOM) who lacked the other diagnostic criteria of PCOS. Participants:Subjects were recruited at the Poznan University of Medical Sciences. Fecal microbial diversity profiles of healthy women (n = 48), women with PCOM (n = 42), and women diagnosed with PCOS using the Rotterdam criteria (n = 73) were analyzed using 16S ribosomal RNA gene sequencing. Results:Lower ? diversity was observed in women with PCOS compared with healthy women. Women with PCOM had a change in ? diversity that was intermediate between that of the other two groups. Regression analyses showed that hyperandrogenism, total testosterone, and hirsutism were negatively correlated with ? diversity. Permutational multivariate analysis of variance in UniFrac distances showed that hyperandrogenism was also correlated with ? diversity. A random forest identified bacteria that discriminated between healthy women and women with PCOS. Conclusion:These results suggest that hyperandrogenism may play a critical role in altering the gut microbiome in women with PCOS.
| S-EPMC6276580 | biostudies-literature
Project description:BackgroundPolycystic Ovary Syndrome (PCOS) often present metabolic disorders and hyperandrogenism (HA), facts that may influence the telomere length (TL).AimsTo compare the absolute TL (aTL) between women with PCOS and control women, and their association with the presence of obesity and HA parameters.Materials and methodsThe PCOS group included 170 unrelated women outpatients and the control group, 64 unrelated donor women. Anthropometric, biochemical-clinical parameters and androgen profile were determined. The PCOS patients were divided accordingly to the presence of obesity and androgenic condition. The aTL was determined from peripheral blood leukocytes by Real Time quantitative PCR.ResultsWomen with PCOS exhibited a significantly longer aTL than controls after age adjustment (p=0.001). A stepwise multivariate linear regression in PCOS women, showed that WC (waist circumference) contributed negatively (b=-0.17) while testosterone levels contributed positively (b=7.24) to aTL. The non-Obese PCOS (noOB-PCOS) presented the longest aTL when compared to controls (p=0.001). Meanwhile, the aTL was significantly higher in the hyperandrogenic PCOS phenotype (HA-PCOS) than in the controls (p=0.001) and non hyperandrogenic PCOS phenotype (NHA-PCOS) (p=0.04). Interestingly, when considering obesity and HA parameters in PCOS, HA exerts the major effect over the aTL as non-obese HA exhibited the lengthiest aTL (23.9 ± 13.13 Kbp). Conversely, the obese NHA patients showed the shortest aTL (16.5 ± 10.59 Kbp).ConclusionsWhilst a shorter aTL could be related to the presence of obesity, a longer aTL would be associated with HA phenotype. These findings suggest a balance between the effect produced by the different metabolic and hormonal components, in PCOS women.
| S-EPMC8162376 | biostudies-literature
Project description:Background: Polycystic ovary syndrome (PCOS) is commonly associated with metabolic abnormalities such as hyperinsulinemia, insulin resistance and obesity. The genetic variants of genes regulating insulin action, expression and regulation are suggested as possible factors involved in development and severity of clinical manifestations in PCOS. Aim: We investigated whether IRS-1Gly972Arg (rs1801278) polymorphism is associated with increased risk of PCOS in Kashmiri women. The correlation of various clinical, metabolic and hormonal markers with rs1801278 single nucleotide polymorphism was analyzed. The genotypic−phenotypic association of clinical manifestations of PCOS with the tested genetic variant was also assessed. Results: There were no significant differences in allele frequency (OR = 0.87, CI = 0.59−1.29, χ2 = 0.456, p = 0.499) or genotypic distribution (χ2 = 3.73, p = 0.15) between PCOS women and controls. No significant association was also found in the dominant (OR = 1.63, χ2 = 0.377, p = 0.53), recessive (OR = 0.79, χ2 = 1.01, p = 0.31) or heterozygote vs. homozygote (OR = 1.34, χ2 = 1.53, p = 0.22) genotype model analysis. The genotype−phenotype correlation analysis showed that the Arg allele was significantly associated with increased central adiposity markers hip circumference (p = 0.012), and body adiposity index BAI (p = 0.002) in the recessive model in PCOS women. The two-hour glucose (p = 0.04) and insulin resistance marker HOMA (p = 0.44) were significantly higher in Arg allele carriers. The androgen excess markers dehydroepiandrosterone sulfate DHEAS (p = 0.02), Ferriman−Gallwey score (p = 0.012), prevalence of acne, alopecia and hirsutism (all p < 0.01) were significantly elevated in the wild-type GG genotype. Conclusions:IRS-1Gly972Arg genetic variant does not increase the risk of PCOS in Kashmiri women. However, this polymorphism is associated with clinical manifestations of insulin resistance, obesity and hyperandrogenism, suggesting its possible role in variable phenotypic manifestations of PCOS.
| S-EPMC9408134 | biostudies-literature
Project description:ContextAndrogen excess may be adrenal and/or ovarian in origin; we hypothesized that a subgroup of patients with polycystic ovarian syndrome (PCOS) may have some degree of abnormal adrenocortical function.ObjectiveThe objective of the study was to evaluate the pituitary adrenal axis with an oral low- and high-dose dexamethasone-suppression test (Liddle's test) in women with PCOS.DesignThis was a case-control study.SettingThe study was conducted at the National Institutes of Health Clinical Center.ParticipantsA total of 38 women with PCOS and 20 healthy volunteers (HV) aged 16-29 years participated in the study.Main outcome measuresUrinary free cortisol (UFC) and 17-hydroxysteroids (17OHS) before and after low- and high-dose dexamethasone and assessment of adrenal volume by computed tomography scan were measured.ResultsTwenty-four-hour urinary 17OHS and UFC were measured during day 1 to day 6 of the Liddle's test. Baseline UFC levels were not different between PCOS and HVs; on the day after the completion of high-dose dexamethasone administration (d 6), UFC was higher in the PCOS group (2.0 ± 0.7 μg/m(2)·d) than the HV group (1.5 ± 0.5) (P = .038). On day 5, 17OHS and UFC were negatively correlated with adrenal volumes (left side, rp = -0.47, P = .009, and rp = -0.61, P < .001, respectively). PCOS patients above the 75th percentile for UFC and/or 17OHS after high-dose dexamethasone (n = 15) had a significantly smaller total adrenal volume (6.9 ± 1.9 cm(3) vs 9.2 ± 1.8 cm(3), P = .003) when compared with the remaining PCOS patients (n = 22), but they did not have worse insulin resistance or hyperandrogenism.ConclusionsIn a subset of young women with PCOS, we detected a pattern of glucocorticoid secretion that mimicked that of patients with micronodular adrenocortical hyperplasia: they had smaller adrenal volumes and higher steroid hormone secretion after dexamethasone compared with the group of PCOS with appropriate response to dexamethasone.
| S-EPMC5010568 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) remains one of the most common endocrine disorder in premenopausal women with an unfavorable metabolic risk profile. Here, we investigate whether biochemical hyperandrogenism, represented by elevated serum free testosterone, resulted in an aberrant circulating microRNA (miRNAs) expression profile and whether miRNAs can identify those PCOS women with metabolic syndrome (MetS). Accordingly, we measured serum levels of miRNAs as well as biochemical markers related to MetS in a case-control study of 42 PCOS patients and 20 Controls. Patients were diagnosed based on the Rotterdam consensus criteria and stratified based on serum free testosterone levels (?0.034 nmol/l) into either a normoandrogenic (n = 23) or hyperandrogenic (n = 19) PCOS group. Overall, hyperandrogenic PCOS women were more insulin resistant compared to normoandrogenic PCOS women and had a higher prevalence of MetS. A total of 750 different miRNAs were analyzed using TaqMan Low-Density Arrays. Altered levels of seven miRNAs (miR-485-3p, -1290, -21-3p, -139-3p, -361-5p, -572, and -143-3p) were observed in PCOS patients when compared with healthy Controls. Stratification of PCOS women revealed that 20 miRNAs were differentially expressed between the three groups. Elevated serum free testosterone levels, adjusted for age and BMI, were significantly associated with five miRNAs (miR-1290, -20a-5p, -139-3p, -433-3p, and -361-5p). Using binary logistic regression and receiver operating characteristic curves (ROC), a combination panel of three miRNAs (miR-361-5p, -1225-3p, and -34-3p) could correctly identify all of the MetS cases within the PCOS group. This study is the first to report comprehensive miRNA profiling in different subgroups of PCOS women with respect to MetS and suggests that circulating miRNAs might be useful as diagnostic biomarkers of MetS for a different subset of PCOS.
| S-EPMC6839444 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is the most common endocrinopathies affecting the early reproductive age in women, whose pathophysiology perplexes many researchers till today. This syndrome is classically categorized by hyperandrogenism and/or hyperandrogenemia, menstrual and ovulatory dysfunction, bulky multi follicular ovaries on Ultrasonography (USG), and metabolic abnormalities such as hyperinsulinemia, dyslipidemia, obesity. The etiopathogenesis of PCOS is not fully elucidated, but it seems that the hypothalamus-pituitary-ovarian axis, ovarian, and/or adrenal androgen secretion may contribute to developing the syndrome. Infertility and poor reproductive health in women's lives are highly associated with elevated levels of androgens. Studies with ovarian theca cells taken from PCOS women have demonstrated increased androgen production due to augmented ovarian steroidogenesis attributed to mainly altered expression of critical enzymes (Cytochrome P450 enzymes: CYP17, CYP21, CYP19, CYP11A) in the steroid hormone biosynthesis pathway. Despite the heterogeneity of PCOS, candidate gene studies are the widely used technique to delineate the genetic variants and analyze for the correlation of androgen biosynthesis pathway and those affecting the secretion or action of insulin with PCOS etiology. Linkage and association studies have predicted the relationship between genetic variants and PCOS risk among families or populations. Several genes have been proposed as playing a role in the etiopathogenesis of PCOS, and the presence of mutations and/or polymorphisms has been discovered, which suggests that PCOS has a vital heritable component. The following review summarizes the influence of polymorphisms in crucial genes of the steroidogenesis pathway leading to intraovarian hyperandrogenism which can result in PCOS.
| S-EPMC8466925 | biostudies-literature
Project description:BackgroundTo investigate the correlation between hyperandrogenism (HA) and insulin resistance (IR) in women with polycystic ovary syndrome (PCOS) by measuring serum total testosterone (TT) using a liquid chromatography and tandem mass spectrometry assay (LC-MS/MS).MethodsThis cohort study included 332 patients with PCOS, 63 patients with IR and 276 with controls. TT levels were measured by LC-MS/MS and chemiluminescent immunoassay (CLIA); glucose and insulin levels were determined by an oral glucose tolerance test (OGTT).ResultsCompared with CLIA, LC-MS/MS differentiated more cases with high TT levels among the non-PCOS subjects with IR In patients with PCOS, LC-MS/MS-based TT levels or a combination with the mFG score detected a significantly higher incidence of HA in subjects with IR identified by hyperinsulinemia (HIN), HOMA-IR or impaired fasting glucose (IFG) than in those without IR Conversely, the IR rates demonstrated by HIN, HOMA-IR, or IFG were remarkably higher in the LC-MS/MS-defined high TT subgroup than in the normal TT subgroup. However, the CLIA platform could not discern a difference in HA incidence between IR and non-IR subgroups or in IR rate between high and normal TT populations. ROC curves also proved that HIN, HOMA-IR, and IFG were positive contributors to HA as measured by LC-MS/MS CONCLUSIONS: The correlation between HA and IR has always been underestimated, partly owing to the less accurate methods previously used to measure TT. HIN, HOMA-IR, and IFG are likely to contribute to the development of HA from a clinical perspective.
| S-EPMC6818543 | biostudies-literature
Project description:Several studies have reported the association between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation to be of uncertain cause: obesity, insulin resistance, or PCOS itself. The aim of the study was to investigate the WBC (white blood cell) count and CRP (C-reactive protein) concentration in women with PCOS and to determine the factors that affect their concentration. The study included 200 women aged 18-40 with PCOS and 105 healthy women as the control group, recruited in the Department of Gynaecological Endocrinology of Medical University in Warsaw from 2016 to 2018. Each patient underwent clinical, biochemical, and ultrasonographic assessments. WBC and CRP were significantly higher in the PCOS group (Z = -2,353, p = 0,019 and Z = -2,453, p = 0,014). WBC positively correlated with serum insulin at 0, 60, and 120?min during the oral glucose tolerance test (INS0: r = 0,221, p = 0,001; INS1: r = 0,194, p = 0,003; INS2: r = 0,022, p = 0,001), testosterone (r = 0,130, p = 0,046), androstenedione (r = 0,212, p = 0,001), and DHEAS (r = 0,178, p = 0,006) and negatively correlated with progesterone (r = -0,204, p = 0,002), estradiol (r = -0,140, p = 0,032), and SHBG (r = -0,308, p < 0,001). CRP positively correlated with insulin concentration in 0, 60, and 120?min during the oral glucose tolerance test (INS0: r = 0,343, p < 0,001; INS1: r = 0,276, p = 0,001; INS2: r = 0,320, p < 001) and negatively correlated with progesterone (r = -0,194, p = 0,030) and SHBG (-0,244, p = 0,005). We also estimated positive correlation between BMI and serum CRP and WBC concentration. Multiple linear regression analysis showed that CRP values are positively associated with BMI (beta = 0,374, p < 0,001) and insulin level (INS1) (beta = 0,282, p = 0,004); and WBC results are negatively associated with SHGB (beta = -0,284, p < 0,001) but positively associated with testosterone (beta = 0,163, p = 0,024) and BMI (beta = 0,157, p = 0,047). PCOS is associated with increased WBC and CRP concentrations. The main predicting factors of increased CRP are BMI and insulin resistance, but there is also a relationship between WBC count in PCOS and androgen concentration itself so that inflammation may be mediated not only through adiposity but also through increased androgen concentration.
| S-EPMC7079227 | biostudies-literature
Project description:BACKGROUND:Polycystic ovary syndrome (PCOS) affects 8% to 13% of reproductive-aged women and is associated with reproductive and metabolic dysfunction. Obesity worsens the presentation of PCOS and weight management (weight loss, maintenance or prevention of excess weight gain) is proposed as an initial treatment strategy, best achieved through lifestyle changes incorporating diet, exercise and behavioural interventions. OBJECTIVES:To assess the effectiveness of lifestyle treatment in improving reproductive, anthropometric (weight and body composition), metabolic and quality of life factors in PCOS. SEARCH METHODS:We searched the Cochrane Gynaecology and Fertility Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, CINAHL and AMED (date of last search March 2018). We also searched controlled trials registries, conference abstracts, relevant journals, reference lists of relevant papers and reviews, and grey literature databases, with no language restrictions applied. SELECTION CRITERIA:Randomised controlled trials (RCTs) comparing lifestyle treatment (diet, exercise, behavioural or combined treatments) to minimal or no treatment in women with PCOS. DATA COLLECTION AND ANALYSIS:Two authors independently selected trials, assessed evidence quality and risk of bias, and extracted data. Our primary outcomes were live birth, miscarriage and pregnancy. We used inverse variance and fixed-effect models in the meta-analyses. We reported dichotomous outcomes as an odds ratio and continuous outcomes as a mean difference (MD) or standardised mean difference (SMD). MAIN RESULTS:We included 15 studies with 498 participants. Ten studies compared physical activity to minimal dietary and behavioural intervention or no intervention. Five studies compared combined dietary, exercise and behavioural intervention to minimal intervention. One study compared behavioural intervention to minimal intervention. Risk of bias varied: eight studies had adequate sequence generation, seven had adequate clinician or outcome assessor blinding, seven had adequate allocation concealment, six had complete outcome data and six were free of selective reporting. No studies assessed the fertility primary outcomes of live birth or miscarriage. No studies reported the secondary reproductive outcome of menstrual regularity, as defined in this review.Lifestyle intervention may improve a secondary (endocrine) reproductive outcome, the free androgen index (FAI) (MD -1.11, 95% confidence interval (CI) -1.96 to -0.26, 6 RCTs, N = 204, I2 = 71%, low-quality evidence). Lifestyle intervention may reduce weight (kg) (MD -1.68 kg, 95% CI -2.66 to -0.70, 9 RCTs, N = 353, I2 = 47%, low-quality evidence). Lifestyle intervention may reduce body mass index (BMI) (kg/m2) (-0.34 kg/m2, 95% CI -0.68 to -0.01, 12 RCTs, N = 434, I2= 0%, low-quality evidence). We are uncertain of the effect of lifestyle intervention on glucose tolerance (glucose outcomes in oral glucose tolerance test) (mmol/L/minute) (SMD -0.02, 95% CI -0.38 to 0.33, 3 RCTs, N = 121, I2 = 0%, low-quality evidence). AUTHORS' CONCLUSIONS:Lifestyle intervention may improve the free androgen index (FAI), weight and BMI in women with PCOS. We are uncertain of the effect of lifestyle intervention on glucose tolerance. There were no studies that looked at the effect of lifestyle intervention on live birth, miscarriage or menstrual regularity. Most studies in this review were of low quality mainly due to high or unclear risk of bias across most domains and high heterogeneity for the FAI outcome.
| S-EPMC6438659 | biostudies-literature