Risk Of Polycystic Ovary Syndrome Research Articles

Molecular determination of progesterone receptor's PROGINS allele (Alu insertion) and its association with the predisposition and susceptibility to polycystic ovary syndrome (PCOS).

Polycystic ovary syndrome, previously known as Stein-Leventhal syndrome, is associated with altered reproductive endocrinology, predisposing a young woman towards the risk of PCOS. It has a prevalence of 6-20% among the reproductive-age women. Progesterone is a key hormone in the pathophysiology of PCOS and patients show diminished response (progesterone resistance), implicating the role of progesterone receptor (PR) as a factor in the disease etiology and prognosis. In this case-control study, we have used mutation-specific PCR (confirmed by Sanger sequencing) to detect the presence of a pathologically significant PR polymorphic variant called as PROGINS. The variant has an Alu insertion in intron G and has two SNPs in exon 4 and exon 5, with all the three aberrations in complete disequilibrium. Our results demonstrated a statistically significant difference in the frequencies of PROGINS between the PCOS patients and healthy controls (p = 0.047). The frequencies of the genotypes CC (A1/A1), CT (A1/A2), and TT (A2/A2) in patients were 74.50%, 20.58%, and 4.90%, and in healthy controls they were 87.28%, 11%, and 1.69%, respectively. Our results put forward two determining factors with regard to PCOS: (i) the frequency of PROGINS allele was significantly higher among PCOS patients compared to the healthy matched controls (0.15 vs 0.07) in the studied population, (ii) the PROGIN allele was significantly associated with the lower levels of serum progesterone in PCOS patients (p < 0.003). The findings are conspicuous as these relate the PROGINS variant to the increased susceptibility of PCOS and might explain the progesterone resistance in patients.

Higher dietary inflammation potential and certain dietary patterns are associated with polycystic ovary syndrome risk in China: A case-control study

The pathogenesis of polycystic ovary syndrome (PCOS) remains unclear; however, inflammation is involved in PCOS progression and can be regulated by diet. We therefore hypothesized that diet may play an important role in the process of PCOS. This study aimed to investigate specific dietary patterns associated with PCOS through a case-control study involving 527 participants and conducted in Fuzhou, China. The dietary inflammatory index (DII) was calculated using a dietary frequency questionnaire, and the dietary pattern was obtained through a principal component analysis (PCA). Logistic regression was used for risk estimation, and the correlations were investigated by partial correlation analysis. The PCA identified a Mediterranean diet, a meat-egg diet, a shellfish-shrimp-dairy diet, and a staple food-soybean diet. The meat-egg (odds ratio [OR] = 1.404; 95% confidence interval [CI], 1.163-1.695) and shellfish-shrimp-dairy (OR = 1.287; 95% CI, 1.057-1.568) diets increased the risk of PCOS. The Mediterranean diet (OR = 0.759; 95% CI, 0.624-0.922) was identified as a protective factor and was negatively correlated with the DII. The DII scores ranged from -4.64 to 4.79 and were positively correlated with the risk of PCOS (OR = 1.141; 95% CI, 1.050-1.240). After adjusting for covariates, the platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and DII were positively correlated in PCOS (P < .001, P = .001, and P < .001, respectively). In conclusion, certain dietary patterns are associated with PCOS. Pro-inflammatory diets increase the risk of PCOS, and the DII was negatively correlated with the Mediterranean diet and positively correlated with the PLR, NLR, and SII.

Association of rs13429458 and rs12478601 Single Nucleotide Polymorphisms of THADA Gene with Polycystic Ovary Syndrome.

BackgroundIt is thought that genetic factors are influential in the etiology of polycystic ovarian syndrome (PCOS), the most frequent endocrinological disorder of females in their reproductive age. This study was carried out to elucidate the association of rs13429458 and rs12478601 single nucleotide polymorphisms (SNPs) of the THADA gene and the risk of the PCOS among a population of Iranian female patients.Materials and MethodsThis case-control study contains 66 infertile women with PCOS (patient group) and 44 healthy women without PCOS (control group) that referred to the IVF Unit of the Infertility Research Center of the Academic Center for Education, Culture and Research (ACECR). The polymerase chain reaction (PCR) was utilized to amplify genome DNA as well as direct sequencing to determine SNPs. The THADA rs12478601 and rs13429458 genotypes were consequently examined with amplification refractory mutation system-PCR (ARMS-PCR).ResultsIn this study, we observed that rs13429458 polymorphism was not associated with PCOS risk in two groups (P=0.42). On the other hand, data analysis indicated that the rs12478601 genotype significantly increased the risk of PCOS in the case group (P=0.032) in compared with control group. We found that the “T” allele of rs12478601 in the THADA gene had a significant relation to PCOS in the case group (odds ratio [OR]: 2.574, 95% confidence interval [CI]: 1.439-4.604, P=0.001).ConclusionThis study has presented further evidence that TT and CT genotype of THADA rs12478601 is associated with a high risk of PCOS.

Lipid ratios and obesity indices are effective predictors of metabolic syndrome in women with polycystic ovary syndrome.

Background:Insulin resistance (IR) is common in women with polycystic ovary syndrome (PCOS). Metabolic syndrome (MS) involves IR, arterial hypertension, dyslipidemia, and visceral fat accumulation. Therefore, fatness indices and blood lipid ratios can be considered as screening markers for MS. Our study aimed to evaluate the predictive potential of selected indirect metabolic risk parameters to identify MS in PCOS.Methods:This cross-sectional study involved 596 women aged 18–40 years, including 404 PCOS patients diagnosed according to the Rotterdam criteria and 192 eumenorrheic controls (CON). Anthropometric and blood pressure measurements were taken, and blood samples were collected to assess glucose metabolism, lipid parameters, and selected hormone levels. Body mass index (BMI), waist-to-height ratio (WHtR), homeostasis model assessment for insulin resistance index (HOMA-IR), visceral adiposity index (VAI), lipid accumulation product (LAP), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides-to-HDL cholesterol ratio (TG/HDL-C) were calculated. MS was assessed using the International Diabetes Federation (IDF) and the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) criteria.Results:MS prevalence was significantly higher in PCOS versus CON. Patients with both MS and PCOS had more unfavorable anthropometric, hormonal, and metabolic profiles versus those with neither MS nor PCOS and versus CON with MS. LAP, TG/HDL-C, VAI, and WHtR were the best markers and strongest indicators of MS in PCOS, and their cut-off values could be useful for early MS detection. MS risk in PCOS increased with elevated levels of these markers and was the highest when TG/HDL-C was used.Conclusions:LAP, TG/HDL-C, VAI, and WHtR are representative markers for MS assessment in PCOS. Their predictive power makes them excellent screening tools for internists and enables acquiring accurate diagnoses using fewer MS markers.

Dietary Total Antioxidant Capacity and Risk of Polycystic Ovary Syndrome: A Case-Control Study.

Background:Among multiple factors that affect the etiology of polycystic ovary syndrome (PCOS), diet has an important contribution. Chronic oxidative stress has also been implicated in the development of PCOS. The present study is an attempt to evaluate dietary total antioxidant capacity (TAC) and its relationship with odds of PCOS in Iran.Materials and Methods:The study was carried out as a case-control study in hospital outpatient clinics, Tehran, Iran. Totally, 310 female participants with a history of PCOS and 602 age-matched controls took part in this study between June 2015 and December 2018. A reproducible and valid 168-item semi-quantitative food frequency inventory was utilized to determine the entire antioxidants of the usual diet in order to calculate dietary TAC. The relationship of dietary TAC with odds of PCOS were assessed adjusting for potential confounders through an estimation of two multivariable conditional regression models. The first tertile was presented as a reference category.Results:In a fully adjusted model, the highest tertile of dietary TAC was associated with a reduced odds of PCOS [odds ratio (OR): 0.81, 95% confidence interval (95% CI): 0.59, 0.96, P for trend: 0.038). In addition, PCOS odds decreased in the highest tertile of α-tocopherol intake (OR: 0.73, 95% CI: 0.56, 0.88, P for trend: 0.023). The adjusted ORs in the highest tertile of vitamin C, β-carotene and magnesium were 0.79 (95% CI: 0.83-0.97), 0.81 (95% CI: 0.67-0.98) and 0.91 (95% CI: 0.55-0.9 8) respectively, with a significant trend.Conclusion:Our results provide evidence that there was a relationship between high TAC diets and lower odds of PCOS.

Evaluation of Prevalence of PCOS and Associated Depression, Nutrition, and Family History: A Questionnaire-based Assessment.

Context:Polycystic ovarian syndrome (PCOS) is a common condition affecting women in the prime of reproductive age. The symptoms include infertility, amenorrhea, hirsutism, obesity, and androgenic alopecia. It is a socially stigmatizing condition and is often associated with depression, poor mental health, and quality of life.Settings and Design:We carried out a questionnaire based cross sectional study that assessed the prevalence of PCOS, collected information on the nutritional and life style related factors. A questionnaire was used to collect information with an intention to assess the prevalence of PCOS and to understand the contribution of life style/nutrition to the risk of PCOS. Student’s t test and Z proportion test were used to assess significance and a ‘p’ value of ≤ 0.05 was considered significant.Results:A total of 972 females completed the questionnaire (mean age:24.37±8.37 years). Majority were from Telangana (n=823;84.67%) and students (690;70.98%). The mean weight was 60.58±13.03 kg and height was 1.78±2.56 m. Sizeable proportion reported irregular menstrual cycle (n=289;29.73%), that they get easily depressed: 283/972 (29.11%), low self-esteem:242/972 (24.90%), insomnia:223/972 (22.94%). A higher proportion of females were diabetic (8/243;3.29%Vs.10/706;1.42%;p=0.02) and non-vegetarian (69/243;28.40%Vs.119/706;16.86%;p=0.0002). No difference in the consumption of processed/fast food, carbonated drinks and lifestyle were noted. A significantly (p=0.0001) higher proportion of females had a positive family history (32/243;13.17%Vs.26/706;3.68%).Conclusion:Higher prevalence of PCOS was noted in young female population. Identifying at-risk individuals and imparting life style, nutrition-based modifications would be beneficial. Furthermore, regular counseling sessions might help tackle depression leading to a better overall physical and mental health.

H6PD Gene Polymorphisms (R453Q and D151A) and Polycystic Ovary Syndrome: A Case-Control Study in A Population of Iranian Kurdish Women.

Background:Polycystic ovary syndrome (PCOS) is known as the most common endocrine and metabolic disorder in the reproductive-age women. Due to the effects of PCOS on the physical and mental health, the investigation of the factors affecting the development of PCOS is crucial. Hexose-6-phosphate dehydrogenase (H6PD) is a microsomal enzyme that catalyzes the first two reactions of the oxidative chain of the pentose phosphate pathway. The present study examined the polymorphisms of the H6PD gene (R453Q and D151A) in PCOS patients of Iranian Kurdish women.Materials and Methods:In this case-control study, a total, of 200 female volunteers in two equal groups participated in our study. The PCOS patients were selected based on the Rotterdam diagnostic criteria. The association of H6PD gene polymorphisms, D151A and R453Q, with the development of PCOS were investigated. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping. Statistical analysis was applied by the SPSS (version 16) software.Results:Statistically significant lower frequencies of AA+AG genotype (37% vs. 55%, P=0.01) and A allele (22.5% vs. 34%, P=0.01) of R453Q were observed in the patients compared to the controls. In the case of D151A, no significant differences were observed in the frequency of genotypes and alleles between the two groups.Conclusion:The findings of this study suggest that variants of H6PD R453Q affect the risk of PCOS.

Association of FSHR and DENND1A polymorphisms with polycystic ovary syndrome: a meta-analysis.

Multiple genetic variants have been studied for years to try to find an association with polycystic ovary syndrome (PCOS). This meta-analysis will investigate if there are associations between increased risk of PCOS and rs6165 polymorphism in follicle stimulating hormone receptor (FSHR) gene and rs2479106 polymorphism in differentially expressed in Differentially Expressed in Normal and Neoplastic Development Isoform 1A (DENND1A) gene. Studies were identified from PubMed library, and case-control studies with correct polymorphisms and available genotype frequencies were included. The statistical analysis is done in Review Manager 5.3, and odds ratio (OR) with corresponding 95% confidence interval (CI) was calculated to see if any association with PCOS exists. In the study of FSHR gene, eight articles with 1539 cases and 1877 controls were included. No relations were found between PCOS and rs6165 polymorphism in neither the allelic (OR=1.07, 95% CI=0.97-1.19, p=0.18), recessive (OR=1.21, 95% CI=0.98-1.50, p=0.07) nor the dominant (OR=1.05, 95% CI=0.91-1.20, p=0.53) model. The rs2479106 polymorphism in DENND1A gene included 10 studies with 3627 cases and 20325 controls. Only the Asian subgroup in the recessive model (OR=1.84, 95% CI=1.19-2.85, p=0.006) showed a positive relation with PCOS, while associations were not found within the overall results in the allelic (OR=1.09, 95% CI=0.98-1.21, p=0.10), recessive (OR=1.26, 95% CI=0.73-2.19, p=0.41) or the dominant (OR=1.31, 95% CI=1.00-1.71, p=0.05) model. This meta-analysis suggests that rs2479106 polymorphism in DENND1A gene is associated with increased risk of PCOS in the Asian population. No relations were found with increased risk of PCOS and rs6165 polymorphism in FSHR gene.

Role of Single Nucleotide Variants in FSHR, GNRHR, ESR2 and LHCGR Genes in Adolescents with Polycystic Ovary Syndrome.

Background: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women, affecting up to 16.6% of reproductive-age women. PCOS symptoms in adolescents comprise oligomenorrhoea/amenorrhoea and biochemical and/or clinical hyperandrogenism. Long-term health risks of PCOS patients include infertility, metabolic syndrome, type 2 diabetes and cardiovascular disease. Genetic factors have been proven to play a role in development of the syndrome and its symptoms. Objective: To investigate single nucleotide variants (SNVs) in the GNRHR, ESR2, LHCGR and FSHR genes in adolescent patients with PCOS and their association with PCOS symptoms. Methods: We conducted a cross-sectional study comprising of 152 adolescents: 63 patients with PCOS, 22 patients at risk of developing PCOS and 67 healthy controls. Participants were recruited from out-patients attending a gynaecologist at the Children’s Clinical University Hospital, Riga, Latvia, between January 2017 and December 2020. Genomic DNA was extracted from whole blood, and SNVs in the GNRHR, ESR2, LHCGR and FSHR genes were genotyped. The distributions of SNV genotypes were compared among the three groups and genotype-phenotype associations within the PCOS group were evaluated. Results: No statistically significant differences were found in the distributions of genotypes for GNRHR (rs104893837), ESR2 (rs4986938), LHCGR (rs2293275) and FSHR (rs6166, rs6165, rs2349415) among PCOS patients, risk patients and healthy controls. Within the PCOS group, ESR2 rs4986938 minor allele homozygous patients had a significantly higher level of total testosterone than major allele homozygous patients and heterozygous patients. A significantly higher total testosterone level was also observed in PCOS patients carrying the LHCGR rs2293275 minor allele compared with major allele homozygous patients. Conclusions: The SNVs ESR2 rs4986938 and LHCGR rs2293275 play a role in the phenotypic characteristics of PCOS. To fully uncover their influence on the development of PCOS and its symptoms, further studies of larger cohorts and a follow up of this study sample through to adulthood are required. Furthermore, studies of adolescent PCOS patients conducted prior to the latest European Society of Human Reproduction and Embryology (ESHRE) criteria (2018) should be re-evaluated as the study groups might include risk patients according to these updated criteria, thereby potentially significantly impacting the published results.

Dietary diversity score is inversely related to the risk of polycystic ovary syndrome in Tehranian women: a case-control study.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age and is affected by various dietary factors. Therefore, this study aimed to investigate the relationship between dietary diversity score (DDS) and the risk of PCOS. Our case-control study was conducted in the summer and autumn of 2019 in Taleghani and Arash hospitals in Tehran, Iran. A total of 494 participants (203 cases and 291 controls) were included in the study. Thereafter, their demographic information, dietary intake, and anthropometric and physical activity assessments were gathered. A validated semi-quantitative food frequency questionnaire was then used to calculate the DDS by scoring 5 food groups. To evaluate the risk of PCOS in association with DDS, the subjects were categorized based on the quartile cut-off points of the DDS. The mean ± SD age of the participants in both the case and control groups was 28.98 ± 5.43 and 30.15 ± 6.21 years, while mean ± SD body mass index was 25.74 ± 5.44 and 23.65 ± 3.90 kg/m2, respectively. The comparison between the case and control groups indicated that total DDS was 5.19 ± 1.19 for the cases and 5.51 ± 1.19 for the controls. The comparison of DDS in the highest versus the lowest quartiles showed a decreased risk of PCOS (p < 0.05). We demonstrated an inverse association between DDS and PCOS compared with the control group. Furthermore, a higher DDS was significantly associated with a lower risk of PCOS (odds ratio = 0.40). Novelty: This is the first investigation on the relationship between DDS and PCOS. Results depicted an inverse relationship between DDS and PCOS.

Clinical Manifestations of Hyperandrogenism and Ovulatory Dysfunction Are Not Associated with His1058 C/T SNP (rs1799817) Polymorphism of Insulin Receptor Gene Tyrosine Kinase Domain in Kashmiri Women with PCOS.

Background Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disorder affecting premenopausal women. Besides primary features like anovulation, hyperandrogenism, and polycystic ovaries, women with PCOS present with multiple metabolic, cardiovascular, and psychological disorders. The etiology is multifactorial and the different genetic variants are suggested to play an important role in pathogenesis. Insulin resistance is a ubiquitous finding in PCOS and SNPs in genes involved in the insulin signaling pathway are possible candidates that can explain the development of clinical manifestations of PCOS. Aim We aimed to investigate the association of INSR His1058 C/T (rs1799817) single nucleotide polymorphism with PCOS in Kashmiri women. The genotypic-phenotypic correlation of the tested SNP with hyperandrogenism, ovulatory dysfunction, and metabolic markers was evaluated. Results The allele frequency (OR = 1.00, 95% CI = 0.67–1.48, χ2 = 0.01, P=0.99) and genotype distribution (χ2 = 3.73, P=0.15) in INSR C/T polymorphism were comparable with controls. No significant association was found with PCOS in dominant (P=0.194), recessive (P=0.442), and homo vs. het. (P=0.5) genotype models. Genotype-phenotype correlation analysis revealed that variant TT genotype had significantly higher HOMA (P=0.029) and reduced insulin sensitivity QUICKI (P=0.037) values. There was no significant variation in the prevalence of hirsutism, acne, alopecia, menstrual disturbances, acanthosis nigricans, and obesity (all P > 0.05) in different INSR C/T genotypes. Conclusion The INSR C/T SNP (rs1799817) does not increase the risk of PCOS in Kashmiri women. This SNP is unlikely to play a significant role in the development and manifestation of clinical symptoms of polycystic ovary syndrome.

Perfluoroalkyl substances (PFAS) in drinking water and risk for polycystic ovarian syndrome, uterine leiomyoma, and endometriosis: A Swedish cohort study.

Perfluorinated substances (PFAS) are chemicals with endocrine disruptive properties that may interfere with the female reproductive system. However, few studies have explored the association between benign gynecological diseases and high PFAS exposure. The aim of this study was to investigate the possible associations between PFAS exposure and subsequent diagnosis of polycystic ovarian syndrome (PCOS), uterine leiomyoma (fibroids), and endometriosis in a cohort exposed to PFAS through drinking water. In 2013, high levels (with sum of PFAS above 10,000ng/L), dominated by perfluorooctanesulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), were found in the drinking water from one of the two waterworks in Ronneby, Sweden. The contamination came from firefighting foams used at a nearby airfield. Females of all ages (n=29,106) who had ever resided in the municipality between 1985 and 2013 formed a cohort. Individual exposure was assessed based on municipality waterworks distribution data linked to annual residential address data; 27% of the females had ever lived at an address with PFAS-contaminated water. Gynecological health outcomes were retrieved from the Swedish National Patient Register. The Cox proportional hazards model was used to estimate the association between exposure and each diagnosis. There were in all 161 cases of PCOS, 1,122 cases of uterine leiomyoma, and 373 cases of endometriosis. In women aged 20-50years (n=18,503), those with the highest estimated PFAS exposure had increased hazard ratios (HR) for PCOS (HR=2.18; 95% confidence interval (CI) 1.43, 3.34) and uterine leiomyoma (HR=1.28; 95% CI 0.95, 1.74). No increased HR for endometriosis was found (HR=0.74; 95% CI 0.42, 1.29). Exposure to high levels of PFAS in drinking water was associated with increased risk of PCOS and possibly uterine leiomyoma, but not endometriosis. The findings for PCOS are consistent with prior studies reporting positive associations between PCOS and PFAS exposure at background levels.

Genetic polymorphisms of reproductive hormones and their receptors in assisted reproduction technology for patients with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women of childbearing, which is defined by the accumulation of multiple, small fluid-filled ovarian cysts without the selection of a single dominant follicle. Most PCOS phenotypes are characterized by the absence of spontaneous ovulation, resistance toward ovulation inductors, the production of a large immature oocytes number, and the high prevalence of ovarian hyperstimulation syndrome, resulting in reduced assisted reproductive technologies (ART) programs effectiveness. The review analyses current data about the relationship between polymorphism genotypes of KISS genes, follicle stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH) and their receptors genes, gonadotropin-releasing hormone (GnRH), estrogen, and progesterone receptors genes, the PCOS risk and the features of ovarian response to stimulation during ART cycles. The use of single nucleotide polymorphisms (SNPs) as prognostic markers of ART programs outcomes would provide a personalized approach to the drugs and doses choice for ovarian stimulation and significantly increase the chance of pregnancy.

CYP17 T/C (rs74357) gene polymorphism contributes to polycystic ovary syndrome susceptibility: evidence from a meta-analysis.

The cytochrome P450 family 17 (CYP17) is associated with hyperandrogenism in women, and the association between CYP17 gene polymorphism and the risk of polycystic ovary syndrome (PCOS) is not definitive. In order to determine whether the CYP17 T/C (rs74357) gene polymorphism is an exposure risk for PCOS, a comprehensive meta-analysis summarizing 19 studies was performed. The pooled odds ratio (OR) and the corresponding 95% CI were measured under five genetic models, and the stratified analyses by ethnicity, Hardy–Weinberg equilibrium, testosterone levels and BMI in controls were carried out to identify the causes of substantial heterogeneity. The overall results validated that the CYP17 T/C (rs74357) gene polymorphism was significantly associated with PCOS risk in four genetic models. Moreover, the outcomes of subgroup analysis by ethnicity indicated that the frequencies of the C allele of CYP17 T/C (rs74357) polymorphism were markedly higher in women from Asia than in Caucasians (T vs C: OR 0.85, 95% CI = 0.74–0.99, P < 0.05). Therefore, these findings suggested that the CYP17 T/C (rs74357) gene polymorphism played an indispensable part in increasing the susceptibility of PCOS when carrying the C allele, which proposed that the polymorphism of the CYP17 gene may be a predictive factor for the risk of PCOS or an important pathway in PCOS-associated metabolic and hormonal dysregulation.

Association Between Angiotensin-Converting Enzyme Gene I/D Polymorphism and Polycystic Ovary Syndrome Susceptibility: a Meta-analysis.

Rec ent studies have suggested a closer association between angiotensin-converting enzyme (ACE) gene polymorphisms and polycystic ovary syndrome (PCOS) risk, but the results were inconsistent. We conducted this meta-analysis to explore the precise associations between ACE gene I/D polymorphism and PCOS risk. Online electronic databases (PubMed, Embase, SCI index, CNKI, and Wanfang) were searched. Odds ratios (ORs) with 95% confidence interval (CIs) were calculated to assess the association between ACE gene I/D polymorphism and PCOS risk. In addition, heterogeneity, accumulative/sensitivity analysis, and publication bias were conducted to check the statistical power. Overall, 12 published case-control studies with 2248 patients and 1759 controls were included according to the criteria. Significant increased risk was found for PCOS susceptibility with I/D mutation (D vs. I: OR = 1.62, 95%CI = 1.24-2.11, P < 0.01, I2 = 86.1%; DD vs. II: OR = 2.10, 95%CI = 1.35-3.27, P < 0.01, I2 = 79.8%; ID + DD vs. II: OR = 1.57, 95%CI = 1.06-2.32, P = 0.02, I2 = 79.3%; DD vs. II + ID: OR = 1.91, 95%CI = 1.39-2.65, P < 0.01, I2 = 79.1%). Furthermore, some similar associations were also observed in subgroups. In summary, the current evidences indicated that ACE gene I/D polymorphism plays an important role in PCOS development, both in Asian and Caucasian descendants.

The Genetic Association of Polycystic Ovary Syndrome and the Risk of Endometrial Cancer: A Mendelian Randomization Study.

The association between polycystic ovary syndrome (PCOS) and endometrial cancer remains unclear. We aimed to investigate the causal association between genetically predicted PCOS and endometrial cancer risk in two ethnic groups through a two-sample Mendelian randomization (MR) approach. Our study includes 13 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for PCOS in Europeans, and another 13 SNPs are used as IVs for PCOS in Asians. Outcome data were obtained from the largest published meta-GWAS of European ancestry to date, as well as from the BioBank Japan Project of Asian ancestry. Our study demonstrates that genetically predicted PCOS is not causally associated with the risk of overall endometrial cancer in either Europeans or Asians (odds ratio (OR) = 0.93, 95% confidence interval (CI) = 0.85–1.01, p = 0.09 and OR = 0.98, 95% CI 0.84–1.13, p = 0.75, respectively). Subgroup analyses according to histotype further illustrate that PCOS might not be associated with the risk of either endometrioid endometrial cancer or non-endometrioid endometrial cancer in European ancestry. No pleiotropy is found in our study, and a sensitivity analysis shows similar results. Our results indicate that genetically predicted PCOS might not be associated with the risk of endometrial cancer.

Correlation Between Serum AMH Levels and Cardiometabolic Indices in PCOS Women.

Introduction:Polycystic ovary syndrome (PCOS) has a predilection for several cardio-metabolic disorders in future. Levels of anti-Mullerian hormone (AMH), a marker of ovarian ageing, are higher in women with PCOS women than in controls. However, whether and how AMH concentrations influence the cardio-metabolic risk in PCOS is yet to be established.Objectives:This study was done to determine the correlation between AMH levels and various cardiometabolic parameters in women with PCOS and to compare AMH levels in PCOS with and without metabolic syndrome (MS).Materials and Methods:In total, 144 women aged 20–40 years and diagnosed as PCOS by the Rotterdam criteria were included in this cross-sectional study. Their anthropometry and blood pressure were recorded. Fasting lipid profile, fasting glucose, fasting insulin, homeostasis model assessment-insulin resistance, total testosterone, and AMH were estimated. The correlation between AMH and cardiometabolic parameters was determined.Results:Serum AMH levels had no correlation with any component of MS. The AMH values were comparable between those with and without MS despite differences in the metabolic profile (11.39 ± 5.31 vs 11.56 ± 5.64 ng/mL, P = 0.861).Conclusion:AMH levels do not correlate with components of MS so it may not be useful as an indicator of cardiovascular risk, insulin resistance, or MS in PCOS.

Pilot study on evaluation and determination of the prevalence of Polycystic Ovarian Syndrome (PCOS) associated gene markers in the South Indian population.

Background:Polycystic ovarian syndrome (PCOS) is typically characterized by a spectrum of manifestations that include menstrual irregularities, anovulation, cysts, hyperandrogenic features like hirsutism, acne, alopecia, and various metabolic complications. The pathology of PCOS is complex and several mechanisms have been potentially involved in the genetic abnormalities/dysfunctions. Hence, the present study aims to examine the prevalence and association of polymorphisms in candidate genes (thyroid adenoma-associated gene [THADA], luteinizing hormone and human chorionic gonadotropin receptor [LHCGR], DENN domain containing 1A [DENND1A], follicle-stimulating hormone receptor [FSHR], Connexin37 [CX37], angiotensin-converting enzyme [ACE], insulin receptor [INSR] and calpain 10 [CAPN10]) in PCOS patients of the South Indian regional population.Methods:The study group included 20 PCOS cases and 10 controls, whose deoxyribonucleic acid (DNA) were genotyped by the polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (RFLP), and PCR product sequencing to determine the prevalence of the DENND1A (rs10818854), LHCGR (rs13405728), FSHR (rs2349415), THADA (rs13429458), CX37 (rs1764391), ACE (rs1799752), INSR (rs1799817), and CAPN10 (rs2975760) polymorphisms. Clinical examinations including anthropometric measurements, biochemical investigations relevant to glucose metabolism, and hormones were measured.Results:A significant difference was observed in the DENND1A (rs10818854) polymorphism between the control and PCOS patients (P = 0.001). The variants of LHCGR, FSHR, THADA, CX37, ACE, INSR, and CAPN10 were not statistically significant with PCOS. The body mass index (BMI) (P = 0.01), triglycerides (P = 0.01), and dehydroepiandrosterone sulfate (DHEAS) (P = 0.05) were significantly different between the PCOS patients and controls. Significant results were observed in rs1799817 single nucleotide polymorphisms (SNP) of INSR with elevated levels of triglycerides and rs10818854 of DENND1A, rs13429458 of THADA, rs2349415 of FSHR with the high levels of DHEAS.Conclusion:In the study population, the presence of rs10818854 of DENND1A polymorphism may be associated with the risk of PCOS and high levels of DHEAS.

Serum spexin, adiponectin and leptin levels in polycystic ovarian syndrome in association with FTO gene polymorphism.

Polycystic ovary syndrome (PCOS) is a complex reproductive endocrinopathy among reproductive-aged women and related with body mass and insulin resistance. Adipocytokines produced by adipose tissue seems to take part in the hormonal and metabolic alterations that arise in PCOS. Fat mass and obesity associated (FTO) gene is linked with body mass index (BMI) and diabetes. Aims - To investigate the association between fat mass related adipocytokines and single nucleotide polymorphisms (SNPs) (rs9939609 T/A) in the FTO gene in women with PCOS. Study design - Cross-sectional study MATERIAL AND METHODS: FTO+rs9939609 gene polymorphism and serum spexin, adiponectin and leptin levels were determined in 91 PCOS women and 86 healthy controls. Study participants were subdivided according to BMI and comparisons were made within each group. Serum spexin levels were not differed between study groups. Serum levels of adiponectin were found to be decreased in PCOS women with BMI lower than 25 kg/m2 (10.1 ± 5.6 vs 14.1 ± 9.1, p = 0.015). Serum leptin levels were elevated in obese PCOS women compared to healthy control group (2197.9 ± 596.3 pg/mL vs 1535.9 ± 812.1 pg/mL, p = 0.001). The prevalence of A risk allele of SNP rs9939609 was more frequent in PCOS patients than in the control group. PCOS risk was found to increase 3 times more in AA genotype when compared with TT genotype (OR = 3.04 95% CI: 1.243-7.309; p = 0.013). Serum adiponectin and leptin levels may serve as independent markers for PCOS diagnosis. Moreover, the FTO+rs9939609 gene polymorphism increase susceptibility to PCOS development independent from serum adipocytokine levels.

Waist circumference, hip circumference, arm span, and waist-to-hip ratio high risk of polycystic ovarian syndrome.

Polycystic ovarian syndrome is a reproductive problem of women with high prevalence cases accompanied by obesity conditions. Obesity condition can be seen from the size of waist circumference, hip circumference, arm span, and waist-to-hip ratio. This study aims to find out the risk factors between waist circumference size, hip circumference, arm span, and waist-to-hip ratio with polycystic ovarian syndrome. This research is an analytical observation using a case-control approach conducted at Sekar Fertility Clinic and Poly Obgyn Dr Moewardi General Hospital Surakarta. Subjects were 150 consisting of 75 polycystic ovarian syndrome women and 75 normal fertile women. Sampling techniques used in this study are purposive sampling, researchers doing anthropometric measurements in the form of waist circumference, hip circumference, arm span, and waist-to-hip ratio simultaneously. The results were analyzed using Statistic Product and Service Solution 25. The results of the study obtained waist circumference with polycystic ovarian syndrome (b = 3.002; CI 95% = 3.41-123.5; p = 0.001), hip circumference (b = -2.671; CI 95% = 0.01-0.37; p = 0.002), arm span (b = 5.318; CI 95% = 32.23-129.58; p < 0.001) and waist-to-hip ratio (b = 1.761; CI 95% = 1.02-33.01; p = 0.047). Waist circumference size, hip circumference, arm span, and waist-to-hip ratio correlate to a high risk of polycystic ovarian syndrome. Arm span is more dominant as an indicator of high risk to polycystic ovarian syndrome compared to waist circumference, hip circumference, and waist-to-hip ratio.