Risk Of Polycystic Ovary Syndrome Research Articles

Polycystic ovary syndrome and cardiovascular risk profile

Polycystic ovary syndrome and cardiovascular risk profile

Association Between Exposure to Multiple Toxic Metals in Follicular Fluid and the Risk of PCOS Among Infertile Women: The Mediating Effect of Metabolic Markers.

Polycystic ovary syndrome (PCOS) severely affects women's fertility and accompanies serious metabolic disturbances, affecting 5%-20% of women of reproductive age globally. We previously found that exposure to toxic metals in the blood raised the risk of PCOS, but the association between exposure to toxic metals and the risk of PCOS in the follicular fluid, the microenvironment for oocyte growth and development in females, and its effect on metabolism has not been reported. This study aimed to evaluate the associations between the concentrations of cadmium (Cd), mercury (Hg), barium (Ba) and arsenic (As) in FF and the risk of PCOS, and to explore the mediating effect of metabolic markers in FF on the above relationship. We conducteda case-control study, including 557 women with PCOS and 651 controls. Ba, Cd, Hg and As levels in FF were measured by ICP-MS, metabolites levels in FF was measured by LC-MS/MS among 168 participants randomly selected from all the participants. Logistic regression models were used to assess the association of a single metal level with the PCOS risk, and linear regression models were used to assess the relationships of a single metal level with clinical phenotype parameters and metabolites levels. Combined effect of metals mixture levels on the risk of PCOS were assessed via weighted quantile sum (WQS) regression and bayesian kernel machine regression (BKMR). Medication analysis was performed to explore the role of metabolic markers on the relationship of toxic metals levels with the risk of PCOS. The exposure levels of Cd, Hg, Ba and As in FF were all positively and significantly associated with the PCOS risk (with respect to the highest vs. lowest tertile group: OR = 1.57, 95% CI = 1.17 ~ 2.12 for Cd, OR = 1.69, 95% CI = 1.22 ~ 2.34 for Hg, OR = 1.76, 95% CI = 1.32 ~ 2.34 for Ba, OR = 1.42, 95% CI = 1.05 ~ 1.91 for As). In addition, levels of metal mixture also significantly correlated with the risk of PCOS, Cd level contributed most to it. Moreover, we observed significant positive relationships between Cd level and LH (β = 0.048, 95% CI = 0.002 ~ 0.094), T (β = 0.077, 95% CI = 0.029 ~ 0.125) and HOMA-IR value (β = 0.060, 95% CI = 0.012 ~ 0.107), as well as Hg level with LH, FSH/LH ratio and TC. Furthermore, we revealed that estrone sulfate, LysoPE 22:6 and N-Undecanoylglycine were significantly and positively mediating the association between Cd level and the risk of PCOS (with mediated proportion of 0.39, 0.24 and 0.35, respectively), and between Hg level and the risk of PCOS (with mediated proportion of 0.29, 0.20 and 0.46, respectively). These highly expressed metabolites significantly enriched in the fatty acid oxidation, steroid hormone biosynthesis and glycerophospholipids metabolism, which may explain the reason why the levels of Cd and Hg in FF associated with the phenotype of PCOS. Ba and As in FF was not found the above phenomenon. Our results suggested that exposure to multiple toxic metals (Cd, Hg, Ba and As) in FF associated with the increased risk of PCOS, Cd was a major contributor. Levels of Cd and Hg in FF significantly associated with the phenotype of PCOS. The above association may result from that Cd and Hg in FF related with the disturbance of fatty acid oxidation, steroid hormone biosynthesis and the glycerophospholipids metabolism.

Polycystic ovary syndrome and endometrial cancer risk: results from a nationwide cohort study.

Most previous studies have found an elevated risk of endometrial cancer among women with polycystic ovary syndrome (PCOS). However, these have highly varying methods for ascertainment of PCOS diagnoses and have limitations such as few exposed women and short follow-up. In this cohort study, we investigated the association between PCOS and endometrial cancer among women born in Denmark between January 1, 1940, and December 31, 1993 (N=1,719,121). Data in this study, including PCOS and endometrial cancer diagnoses and covariates, were derived from nationwide registers. We used cox proportional hazard regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 7862 endometrial cancer cases were identified during 23.7 years of follow-up (inter quartile range 37.7-61.9). We found an increased risk of endometrial cancer among women with PCOS compared with women without PCOS (HR: 3.02, 95% CI; 2.03-4.49). The risk was increased for premenopausal women (HR5.82, 95% CI: 3.64-9.30) whereas no marked association was seen for postmenopausal women. However, for postmenopausal women, results were limited by few cases and young age at end of follow-up. Mounting evidence of an increased risk for endometrial cancer among women with PCOS reinforces the need for prevention and early detection.

Causal relationships between modifiable risk factors and polycystic ovary syndrome: a comprehensive Mendelian randomization study.

Polycystic Ovary Syndrome (PCOS) is a heritable condition with an as yet unclear etiology. Various factors, such as genetics, lifestyle, environment, inflammation, insulin resistance, hyperandrogenism, iron metabolism, and gut microbiota, have been proposed as potential contributors to PCOS. Nevertheless, a systematic assessment of modifiable risk factors and their causal effects on PCOS is lacking. This study aims to establish a comprehensive profile of modifiable risk factors for PCOS by utilizing a two-sample Mendelian Randomization (MR) framework. After identifying over 400 modifiable risk factors, we employed a two-sample MR approach, including the Inverse Variance Weighted (IVW) method, Weighted Median method, and MR-Egger, to investigate their causal associations with PCOS. The reliability of our estimates underwent rigorous examination through sensitivity analyses, encompassing Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots. We discovered that factors such as smoking per day, smoking initiation, body mass index, basal metabolic rate, waist-to-hip ratio, whole body fat mass, trunk fat mass, overall health rating, docosahexaenoic acid (DHA) (22:6n-3) in blood, monounsaturated fatty acids, other polyunsaturated fatty acids apart from 18:2 in blood, omega-3 fatty acids, ratio of bisallylic groups to double bonds, omega-9 and saturated fatty acids, total lipids in medium VLDL, phospholipids in medium VLDL, phospholipids in very large HDL, triglycerides in very large HDL, the genus Oscillibacter, the genus Alistipes, the genus Ruminiclostridium 9, the class Mollicutes, and the phylum Tenericutes, showed a significant effect on heightening genetic susceptibility of PCOS. In contrast, factors including fasting insulin interaction with body mass index, sex hormone-binding globulin, iron, ferritin, SDF1a, college or university degree, years of schooling, household income, the genus Enterorhabdus, the family Bifidobacteriaceae, the order Bifidobacteriales, the class Actinobacteria, and the phylum Actinobacteria were determined to reduce risk of PCOS. This study innovatively employs the MR method to assess causal relationships between 400 modifiable risk factors and the susceptibility of PCOS risk. It supports causal links between factors like smoking, BMI, and various blood lipid levels and PCOS. These findings offer novel insights into potential strategies for the management and treatment of PCOS.

Causal Relationships between Homocysteine and the Polycystic Ovary Syndrome: A Mendelian Randomization Analysis.

Polycystic ovary syndrome (PCOS) is an endocrine disease attributed to multiple genetic variants and environmental factors. We aimed to find the causal association of homocysteine (Hcy) with PCOS. A two-sample Mendelian randomization (MR) analysis was performed. We selected 14 single-nucleotide polymorphisms (SNPs) as instrumental variables to predict the risk of PCOS from genome-wide association studies (GWAS). The summary statistics of PCOS were obtained from 3 large genome-wide association studies in the European population, involving 4,138 cases and 20,129 controls, 3,609 cases and 229,788 controls, 994 cases and 165,817 controls, separately. The IVM analyses revealed that plasma Hcy levels were not causally associated with the risk of PCOS in the meta-analysis (combined effect = 1.032, 95% confidence interval (CI): 0.885-1.203, p=0.688). There was no sufficient evidence to support the causal association of the Hcy with the risk of PCOS.

Causal association between low vitamin D and polycystic ovary syndrome: a bidirectional mendelian randomization study

BackgroundRecent studies have revealed the correlation between serum vitamin D (VD) level and polycystic ovary syndrome (PCOS), but the causality and specific mechanisms remain uncertain.ObjectiveWe aimed to investigate the cause-effect relationship between serum VD and PCOS, and the role of testosterone in the related pathological mechanisms.MethodsWe assessed the causality between serum VD and PCOS by using genome-wide association studies (GWAS) data in a bidirectional two-sample Mendelian randomization (TS-MR) analysis. Subsequently, a MR mediation analysis was conducted to examine the mediating action of testosterone in the causality between serum VD and PCOS. Ultimately, we integrated GWAS data with cis-expression quantitative loci (cis-eQTLs) data for gene annotation, and used the potentially related genes for functional enrichment analysis to assess the involvement of testosterone and the potential mechanisms.ResultsTS-MR analysis showed that individuals with lower level of serum VD were more likely to develop PCOS (OR = 0.750, 95% CI: 0.587–0.959, P = 0.022). MR mediation analysis uncovered indirect causal effect of serum VD level on the risk of PCOS via testosterone (OR = 0.983, 95% CI: 0.968–0.998, P = 0.025). Functional enrichment analysis showed that several pathways may be involved in the VD-testosterone-PCOS axis, such as steroid hormone biosynthesis and autophagy process.ConclusionOur findings suggest that genetically predicted lower serum VD level may cause a higher risk of developing PCOS, which may be mediated by increased testosterone production.

Association between Dietary Inflammatory Index (DII) and the Risk of Polycystic Ovary Syndrome: A Case-Control Study

Background: Polycystic ovary syndrome (PCOS) is an inflammation-related condition and a common metabolic disorder in women at fertility ages. The Dietary Inflammatory Index (DII) is a validated nutritional tool for estimating the inflammatory potential of the diet. It is assumed that a high DII score (indicating a predominantly inflammatory diet) has an association with higher odds of PCOS. The current study aimed to investigate the association between DII and PCOS risk in women. Methods: This case-control study was conducted in 2019-2020 on 120 newly-diagnosed PCOS cases and 120 healthy controls aged 18-45 years in Khorramabad, Iran. DII was estimated based on a validated 168-item Food Frequency Questionnaire (FFQ). Results: The mean±SD of DII in PCOS patients was 0.40±2.09, while it was 0.45±1.92 in the control group (P<0.001). There was a positive association between increasing DII score and the risk of PCOS (odds ratio= 2.41; 95%CI: 1.15-5.02, P for trend =0.006) in the crude model as the fourth quartile was compared with the lowest one. This association was still significant in several models after adjusting for age and energy intake (P for trend <0.001), in the model adjusted for the physical activity level, education status, and family history of PCOS (P for trend=0.003), and also after additional adjustment for BMI (P for trend= 0.003). Conclusions: The present study revealed that consuming more pro-inflammatory diets with higher DII scores is related to an increased risk of PCOS.

Bioinformatics-based analysis of potential therapeutic target genes for polycystic ovary syndrome.

The purpose of this study was to screen differentially expressed genes in PCOS using gene chip data and investigate the biological functions of these DEGs in PCOS. Additionally, the study aimed to analyze the potential clinical significance of these genes using clinical data. In this study, we first screened the DEGs related to PCOS by using the gene chip data (GSE5090) from GEO database. Target gene prediction software was used to predict the target genes for these DEGs, and their functional enrichment was analysed. Subsequently, the STRING online tool and Cytoscape software were utilized to identify key genes by constructing protein-protein interaction networks (PPI). In the analysis of the GSE5090 dataset, seventeen differentially expressed genes (DEGs) were identified. Functional enrichment analysis revealed that these DEGs are predominantly associated with biological functions related to polycystic ovary syndrome (PCOS). Moreover, the tissue-specific expression analysis highlighted immune system markers, with a notable difference observed in 18 of these markers, accounting for 20.5% of the total. By constructing PPI networks and key gene regulatory networks, a total of three genes (RPL13, LEP, and ANXA1) were identified as key genes. In addition, the column-line graphical model performed well in predicting the risk of PCOS. Using ROC curves, the model proved to be effective in diagnosis. This study represents the first application of a bioinformatics approach to identify and confirm high expression levels of RPL13, LEP, and ANXA1 in patients with Polycystic Ovary Syndrome (PCOS). These key genes-RPL13, LEP, and ANXA1-may present viable targets for therapeutic interventions in PCOS, underscoring their potential clinical importance.

Plastic-related endocrine disrupting chemicals significantly related to the increased risk of estrogen-dependent diseases in women

ObjectiveTo evaluate the association between exposure to plastic-related endocrine-disrupting chemicals (EDCs), specifically Bisphenol A (BPA), Phthalates, Cadmium, and Lead, and the risk of estrogen-dependent diseases (EDDs) such as polycystic ovary syndrome (PCOS), endometriosis, or endometrial cancer by conducting a meta-analysis of relevant studies. MethodsPubMed, Web of Science, and Cochrane Library databases were used for literature retrieval of articles published until the 21st of April 2023. Literature that evaluated the association between BPA, phthalates, cadmium, and/or lead exposure and the risk of PCOS, endometriosis, or endometrial cancer development or exacerbation were included in our analysis. STATA/MP 17.0 was used for all statistical analyses. ResultsOverall, 22 articles were included in our meta-analysis with a total of 83,641 subjects all of whom were females aged between 18 and 83 years old. The overall effect size of each study was as follows: endometriosis risk in relation to BPA exposure ES 1.82 (95% CI; 1.50, 2.20). BPA and PCOS risk ES 1.61 (95% CI; 1.39, 1.85). Phthalate metabolites and endometriosis risk; MBP ES 1.07 (95% CI; 0.86, 1.33), MEP ES 1.05 (95% CI; 0.87, 1.28), MEHP ES 1.15 (95% CI; 0.67, 1.98), MBzP ES 0.97 (95% CI; 0.63, 1.49), MEOHP ES 1.87 (95% CI; 1.21, 2.87), and MEHHP ES 1.98 (95% CI; 1.32, 2.98). Cadmium exposure and endometrial cancer risk ES 1.14 (95% CI; 0.92, 1.41). Cadmium exposure and the risk of endometriosis ES 2.54 (95% CI; 1.71, 3.77). Lead exposure and the risk of endometriosis ES 1.74 (95% CI; 1.13, 2.69). ConclusionIncreased serum, urinary, or dietary concentration of MBzP and MEHP in women is significantly associated with endometriosis risk. Increased cadmium concentration is associated with endometrial cancer risk.

Associations of Childhood Adiposity and Cardiometabolic Biomarkers With Adolescent PCOS.

Polycystic Ovary Syndrome (PCOS) is common among females, with significant metabolic and reproductive comorbidities. We describe PCOS development in a pediatric population. We assessed cardiometabolic biomarkers and adiposity at the midchildhood (mean 7.9 y), early teen (mean 13.1 y), and midteen (mean 17.8 y) visits among 417 females in the prospective Project Viva cohort. We defined PCOS via self-reported diagnosis or ovulatory dysfunction with hyperandrogenism in midlate adolescence. We used multivariable logistic regression to assess associations of metabolic and adiposity markers at each visit with PCOS. Adolescents with PCOS (n = 56, 13%) versus without had higher mean (SD) BMI z-score and truncal fat mass at the midchildhood (0.66 [0.99] vs 0.30 [1.04]; 3.5 kg [2.6] vs 2.7 [1.5]), early teen (0.88 [1.01] vs 0.25 [1.08]; 9.4 kg [6.7] vs 6.1 [3.4]), and midteen (0.78 [1.03] vs 0.33 [0.97]; 11.6 kg [7.2] vs 9.1 [4.9]) visits as well as lower adiponectin to leptin ratio at the early (0.65 [0.69] vs 1.04 [0.97]) and midteen (0.33 [0.26] vs 0.75 [1.21]) visits. In models adjusted for maternal PCOS, education and child race and ethnicity (social factors), we found higher odds of PCOS per 1-SD increase in truncal fat at midchildhood (odds ratio [OR] 1.42; 95% confidence interval [CI] 1.03-1.95) and early teen visits (OR 1.61; 95% CI 1.14-2.28) and lower odds per 1-SD increase in adiponectin/leptin ratio at the midteen visit (OR 0.14; 95% CI 0.03-0.58). Childhood excess adiposity and adipose tissue dysfunction may be a first signs of later PCOS risk.

Genetic variants of KISS1 gene in association with polycystic ovary syndrome– A meta-analysis

Polycystic ovary syndrome (PCOS) is a widely diagnosed syndrome associated with clinical and metabolic manifestations and even many cases of infertility. Sexual hormone imbalance can be considered as PCOS causal factor. Thus, kisspeptin (KISS1) regulating gonadotropin-releasing hormone (GnRH) levels plays a critical role in this syndrome. This study aimed to investigate the association of KISS1 genetic polymorphisms with PCOS using meta-analysis protocols. In accordance with PRISMA guidelines, systematic search of scientific databases was conducted to find included articles and then meta-analysis was performed using Review Manager 5.4 in dominant, recessive, and allelic models of inheritance. This meta-analysis included 2165 PCOS patients and 2301 healthy reproductive-aged female genotyped for five different polymorphisms of KISS1. In recessive and allelic models, three genetic variations specifically showed significant association with PCOS. This concerns rs12998 (G → A) which was proved as associated with higher risk of PCOS in recessive (p = 0.0002) and allelic models (P = 0.02). In addition, rs372790354 despite the small number of studies was associated with this syndrome in allelic model (P = 0.03). In additive model, rs4889 was shown as associated with higher PCOS risk (P = 0.02). This meta-analysis suggests rs4889, rs12998 and rs372790354 genetic variations in KISS1 as risk factors of PCOS. Results will improve our knowledge about PCOS and form a basis for future trials trying to find new markers for its prognosis and therapy.

Assessing the clinical diagnostic value of anti-Müllerian hormone in polycystic ovarian syndrome and its correlation with clinical and metabolism indicators

BackgroundThis study investigated the association between Anti-Müllerian Hormone (AMH) and relevant metabolic parameters and assessed its predictive value in the clinical diagnosis of polycystic ovarian syndrome (PCOS).MethodsA total of 421 women aged 20–37 years were allocated to the PCOS (n = 168) and control (n = 253) groups, and their metabolic and hormonal parameters were compared. Spearman correlation analysis was conducted to investigate associations, binary logistic regression was used to determine PCOS risk factors, and receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of AMH in diagnosing PCOS.ResultsThe PCOS group demonstrated significantly higher blood lipid, luteinizing hormone (LH), and AMH levels than the control group. Glucose and lipid metabolism and hormonal disorders in the PCOS group were more significant than in the control group among individuals with and without obesity. LH, TSTO, and AMH were identified as independent risk factors for PCOS. AMH along with LH, and antral follicle count demonstrated a high predictive value for diagnosing PCOS.ConclusionAMH exhibited robust diagnostic use for identifying PCOS and could be considered a marker for screening PCOS to improve PCOS diagnostic accuracy. Attention should be paid to the effect of glucose and lipid metabolism on the hormonal and related parameters of PCOS populations.

The use of an Internet resource in young people to identify female students at risk for polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a polygenic endocrine disorder caused by both genetic and epigenetic factors. Depending on the period of a woman’s life, the clinical picture, diagnosis, and treatment tactics of the disease are different. The syndrome has a set of reproductive, metabolic, and psychological features. Objective. To study the prevalence of PCOS among female students and to evaluate the effectiveness of using Internet platforms in identifying the manifestations that characterize reproductive health disorders. Subjects and methods. A total of 330 respondents studying in the higher educational establishments of Khabarovsk were interviewed using the Google Forms platform in October to December 2021 in order to identify whether they had irregular menstruation, hyperandrogenism, which was followed by an examination and verification of the diagnosis of PCOS in an outpatient setting. Results. According to the survey results, 87.58% of the respondents did not plan pregnancy in the next 2 years, so infertility as one of the PCOS symptoms did not cause anxiety in them. According to the survey among the female students with an irregular menstrual cycle, the incidence rate of PCOS was 24.7%. Conclusion. In our opinion, the active detection of PCOS in patients with an irregular menstrual cycle among young people using Internet resources allows them to focus their attention on reproductive health disorders and on the need to consult a gynecologist.

Association Between rs2278426 Polymorphism of the ANGPTL8 Gene and Polycystic Ovary Syndrome.

To study the relationship between the single nucleotide polymorphism (SNP) rs2278426 in the angiopoietin-like protein 8 gene (ANGPTL8) and polycystic ovary syndrome (PCOS). A total of 122 patients with PCOS and 108 controls were recruited for comparison of glucose, lipid, insulin, sex hormone, and ANGPTL8 levels. Polymerase chain reaction (PCR) and gene sequencing were performed for comparison of the frequency of the CC, CT, and TT rs2278426 genotypes and the rs2278426 allele distributions between the PCOS and control groups and between the obese and non-obese subgroups of the PCOS and control groups. The frequency of the T allele was significantly higher in the PCOS group than that in the controls (P = 0.037). In the dominant genetic model, the proportion of the CT+TT genotype in the PCOS group was significantly higher than that in the controls (P = 0.047). Subgroup analysis demonstrated that the T allele proportion was significantly higher in obese PCOS group than obese control group (P = 0.027). PCOS with the CT+TT genotype had significantly higher body mass index (BMI; P = 0.001), triglyceride (TG; P = 0.005), homeostasis model assessment of insulin resistance (HOMA-IR; P = 0.035), testosterone (P = 0.041), and ANGPTL8 (P = 0.037) levels and significantly lower high-density lipoprotein (HDL) levels (P = 0.025) than PCOS with the CC genotype. Obese PCOS group with the CT+TT genotype had significantly higher TG (P = 0.015), luteinizing hormone (LH; P = 0.030), fasting insulin (FINS; P = 0.039), HOMA-IR (P = 0.018), and ANGPTL8 (P = 0.049) levels than obese PCOS group with the CC genotype. Polymorphisms of rs2278426 may induce glycolipid metabolic disorders by affecting ANGPTL8 levels and functions in Han Chinese females with obesity from the Shandong region, increasing the risk of PCOS in this population.

IGF2BP2 and IGFBP3 Genotypes, Haplotypes, and Genetic Models Studies in Polycystic Ovary Syndrome.

Insulin resistance has been correlated with the genetic diversity within the insulin-like binding proteins genes. Moreover, insulin resistance is one of the key characteristics of the widespread reproductive endocrine condition known as polycystic ovarian syndrome (PCOS). Hence, this study is aimed to determine the association between IGFBP3 and IGF2BP2 gene variants and PCOS risk. A total of 300 subjects (150 PCOS cases diagnosed based on Rotterdam ESHRE/ASRM consensus criteria and 150 healthy subjects) were recruited in this case-control cross-sectional study. Tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR) was used for genotyping rs11705701, whereas genotyping of rs1470579 and rs2854744 was done employing PCR-restriction fragment length polymorphism (PCR-RFLP) technique. The CC and AA+AC genotypes of rs1470579 conferred an increased risk of PCOS in our population. Regarding the rs2854744, an increased risk of PCOS was observed under the codominant homozygous (TT vs. GG) model by 2.54 fold. The C allele of rs1470579 and T allele of rs2854744 enhanced PCOS risk by 1.97 and 1.46 folds, respectively. Haplotype analysis showed that the Ars1470579Ars11705701 haplotype conferred a decreased risk of PCOS (odds ratio = 0.53, 95% confidence interval = 0.34-0.83, p = 0.006). The AC/GG/GT, AA/GA/GT, AC/GA/GG, and AC/GA/GT genotype combinations of rs1470579/rs11705701/rs2854744 were associated with a decreased risk of the disease. IGF2BP2 rs1470579 and IGFBP3 rs2854744 enhanced PCOS susceptibility in a Southeastern Iranian population. Further investigation involving larger cohorts representing diverse ethnic backgrounds is needed to confirm the current findings.

Genome-wide association study (GWAS) identified PCOS susceptibility variants and replicates reported risk variants.

Genetic predisposition and environmental factors are considered risk factors for polycystic ovary syndrome (PCOS). Genome-wide association studies (GWAS) have been reported from various subpopulations to evaluate SNPs associated with PCOS risk. No PCOS-associated GWAS study has been reported from India so far. The current study was conducted to identify the PCOS-susceptible loci among the North Indian population and to validate the significant loci reported by previous GWAS studies. A total of 272 participants with 134 PCOS patients and 138 age-matchedhealthy controls were recruited. Genomic DNA was isolated and genotyped by using Infinium Global Screening Array v3.0 microchip considering HWE 10e-5 statistically significant. A total of fifteen markers have been identified as candidate PCOS risk factors. Only two SNPs, namely rs17186366 and rs11171739 have been identified through replication analysis while comparing the previously reported PCOS GWAS data. In-silico analysis was performed to study the functional impact of identified significant genes for gene ontology, pathways related to gene set, and cluster analysis to determine protein-protein interaction among genes or gene products. The study suggests that multiple variants play an important role in PCOS pathogenesis and emphasizes the importance of further genetic studies among Indian subpopulations.The study also validates two previously reported SNPs in the Indian population. What this study adds to clinical work Study summarizes the importance of candidate gene markers validated by replication and in-silico functional study, significantly involved in PCOS pathogenesis in the studied population. These markers can be used in the future as diagnostic markers for clinical phenotype identification.

Mineral Metabolism and Polycystic Ovary Syndrome and Metabolic Risk Factors: A Mendelian Randomization Study.

Observational investigations recommend that mineral supplements were associated with a higher risk of polycystic ovary syndrome (PCOS) and its risk factors (insulin resistance, hyperandrogenism, and obesity), but the relationship with risk of PCOS, hyperandrogenism, obesity, and insulin resistance was unclear. This study was to investigate the potential causal impact of genetically predicted levels of magnesium (Mg), calcium (Ca), selenium (Se), zinc (Zn), iron (Fe), and omega-3 (ω-3) on polycystic ovary syndrome (PCOS) and its associated risk factors. A two-sample Mendelian randomization (MR) analysis was conducted. The genetic variations obtained from GWAS of individuals with European ancestry were found to be associated with the genetically predicted levels of Ca, Mg, Zn, Se, Fe, or ω-3. The data obtained from the FinnGen Consortium and MAGIC were utilized for the outcome of GWAS. The study found that there was a correlation between genetically predicted higher levels of Se and a reduced risk of insulin resistance, with a decrease of 2.2% according to random-effect IVW (OR 0.978, 95% CI 0.960-0.996, p = 0.015). The association between genetically determined mineral levels and PCOS was found to be limited, with an odds ratio (OR) ranging from 0.875 (95% CI: 0.637-1.202, p value = 0.411) for Ca. Limited scientific proof was found for the efficacy of other genetically determined mineral levels on hyperandrogenism, obesity, and insulin resistance. These findings suggested a causal relationship between genetically predicted higher levels of Se and a reduced risk of insulin resistance. Nonetheless, there is limited evidence supporting a causal association between various genetically determined mineral levels and the risk factors associated with PCOS.

Heme oxygenase 2 genetic variants alter hormonal and metabolic traits in polycystic ovary syndrome.

Oxidative stress and metabolic disorders are involved in the pathogenesis of polycystic ovary syndrome (PCOS). Heme oxygenase 2 (HMOX2) plays a critical role in preserving heme metabolism as well as in modulating glycolipid metabolism, oxidative stress, and inflammation. This study examined the correlation between HMOX2 G554A (rs1051308) and A-42G (rs2270363) genetic variants with the risk of PCOS and assessed the effects of these genotypes on clinical, hormonal, metabolic, and oxidative stress indices using a case-control design that included 1014 patients with PCOS and 806 control participants. We found that the allelic and genotypic frequencies of the HMOX2 G554A and A-42G polymorphisms were comparable between the PCOS and control groups in Chinese women (P > 0.05). Nevertheless, it was discovered that patients with the AA or AG genotype of A-42G polymorphism had notably elevated levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH ratio, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (apo)B, and/or apoB/apoA1 ratio than those with the GG genotypes (P < 0.05). Patients with the GG or AG genotype of G554A polymorphism had elevated serum levels of LH, FSH, E2, LH/FSH ratio, TC, HDL-C, LDL-C, apoB, and/or apoB/apoA1 ratio and lower 2-h glucose concentration compared with those with the AA genotype (P < 0.05). Our findings indicate a potential association between the genetic variants and endocrine abnormalities in the reproductive system and metabolic irregularities in glycolipid levels in patients, thus suggesting their potential role in the pathogenesis of PCOS.

Gut microbiota and polycystic ovary syndrome, focus on genetic associations: a bidirectional Mendelian randomization study.

The contribution of gut microbiota to the pathogenesis of polycystic ovary syndrome (PCOS) is controversial. The causal relationship to this question is worth an in-depth comprehensive of known single nucleotide polymorphisms associated with gut microbiota. We conducted bidirectional Mendelian randomization (MR) utilizing instrumental variables associated with gut microbiota (N = 18,340) from MiBioGen GWAS to assess their impact on PCOS risk in the FinnGen GWAS (27,943 PCOS cases and 162,936 controls). Two-sample MR using inverse variance weighting (IVW) was undertaken, followed by the weighted median, weighted mode, and MR-Egger regression. In a subsample, we replicated our findings using the meta-analysis PCOS consortium (10,074 cases and 103,164 controls) from European ancestry. IVWMR results suggested that six gut microbiota were causally associated with PCOS features. After adjusting BMI, SHBG, fasting insulin, testosterone, and alcohol intake frequency, the effect sizes were significantly reduced. Reverse MR analysis revealed that the effects of PCOS features on 13 gut microbiota no longer remained significant after sensitivity analysis and Bonferroni corrections. MR replication analysis was consistent and the results suggest that gut microbiota was likely not an independent cause of PCOS. Our findings did not support the causal relationships between the gut microbiota and PCOS features at the genetic level. More comprehensive genome-wide association studies of the gut microbiota and PCOS are warranted to confirm their genetic relationship. This study contains 3533 words, 0 tables, and six figures in the text as well as night supplementary files and 0 supplementary figures in the Supplementary material.

Increased GPC4 and clusterin associated with insulin resistance in patients with PCOS.

The aim of the study was to investigate the changes in serum glypican 4 (GPC4) and clusterin (CLU) levels in patients with polycystic ovary syndrome (PCOS) as well as their correlation with sex hormones and metabolic parameters. A total of 40 PCOS patients and 40 age-matched healthy women were selected. Serum GPC4 and CLU levels were compared between the PCOS and control groups, and binary logistic regression was used to analyze the relative risk of PCOS at different tertiles of serum GPC4 and CLU concentrations. Stepwise linear regression was used to identify the factors influencing serum GPC4 and CLU levels in PCOS patients. Serum GPC4 (1.82 ± 0.49 vs 1.30 ± 0.61 ng/mL, P < 0.001) and CLU (468.79 ± 92.85 vs 228.59 ± 82.42 µg/mL, P < 0.001) were significantly higher in PCOS patients than in healthy women after adjustment for body mass index (BMI). In the PCOS group, serum GPC4 was positively correlated with follicle-stimulating hormone, fasting plasma glucose (FPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride, and CLU (P < 0.05), whereas serum CLU was positively correlated with BMI, FPG, FINS, and HOMA-IR (P < 0.05). Multiple stepwise linear regression analysis showed that HOMA-IR was independently associated with serum GPC4, and BMI and HOMA-IR were independently associated with CLU (P < 0.05). Serum GPC4 and CLU levels were significantly higher in PCOS patients than in healthy women, suggesting that GPC4 and CLU may be markers associated with insulin resistance in women with PCOS.