Replication study and meta-analysis of selected genetic variants and polycystic ovary syndrome susceptibility in Asian population

2021 ◽  
Author(s):  
Pengcheng Wan ◽  
Linghan Meng ◽  
Chao Huang ◽  
Baosheng Dai ◽  
Yuchen Jin ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Genetic Variants ◽  
Polycystic Ovary ◽  
Meta Analysis ◽  
Asian Population ◽  
Replication Study ◽  
Ovary Syndrome

scholarly journals Variants in SULT2A1 Affect the DHEA Sulphate to DHEA Ratio in Patients With Polycystic Ovary Syndrome But Not the Hyperandrogenic Phenotype

2013 ◽  
Vol 98 (9) ◽  
pp. 3848-3855 ◽  
Author(s):  
Yvonne V. Louwers ◽  
Frank H. de Jong ◽  
Nathalie A. A. van Herwaarden ◽  
Lisette Stolk ◽  
Bart C. J. M. Fauser ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Genetic Variants ◽  
Polycystic Ovary ◽  
Meta Analysis ◽  
Significant Snps ◽  
Serum Levels ◽  
Dehydroepiandrosterone Sulfate ◽  
Nucleotide Polymorphisms ◽  
Ovary Syndrome ◽  
Hormone Levels

Context: Because of the elevated dehydroepiandrosterone sulfate (DHEAS) levels in polycystic ovary syndrome (PCOS) and the heritability of DHEAS serum levels, genes encoding the enzymes that control the sulfation of dehydroepiandrosterone (DHEA) to DHEAS and vice versa are obvious candidate genes to explain part of the heritability of PCOS. Objective: The objective of the study was to determine the role of genetic variants in sulfotransferase (SULT2A1), 3-phosphoadenosine 5-phosphosulfate synthase isoform 2 (PAPSS2), and steroid sulfatase (STS) in PCOS and in hormone levels related to the hyperandrogenic phenotype of PCOS. Design: This was a candidate-gene study. Patients: The discovery set consisted of 582 patients and 2017 controls. Main Outcome Measures: A pruned subset of 28 single-nucleotide polymorphisms (SNPs) in SULT2A1, PAPSS2, and STS was generated based on pairwise genotypic correlation. Association with PCOS was tested, and we studied whether the SNPs modulate DHEAS levels, DHEA levels, and their ratio in PCOS. Significant SNPs were replicated in an independent sample of patients. Results: None of the SNPs in SULT2A1, PAPSS2, and STS constituted risk alleles for PCOS. SNP rs2910397 in SULT2A1 decreased the DHEAS to DHEA ratio in PCOS by 5% in the discovery sample. Meta-analysis of discovery and replication sample resulted in a combined effect of −0.095 (P = .027). However, carrying the minor T allele did not contribute to differences in the hyperandrogenic phenotype, including the levels of T and androstenedione, of PCOS patients. Conclusions: Genetic variants in SULT2A1, PAPSS2, and STS do not predispose to PCOS. Although a variant in SULT2A1 decreased the DHEAS to DHEA ratio, no changes in other androgenic hormone levels were observed.

scholarly journals Cross-Ethnic Meta-Analysis of Genetic Variants for Polycystic Ovary Syndrome

2013 ◽  
Vol 98 (12) ◽  
pp. E2006-E2012 ◽  
Author(s):  
Yvonne V. Louwers ◽  
Lisette Stolk ◽  
André G. Uitterlinden ◽  
Joop S. E. Laven
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Genetic Variants ◽  
Polycystic Ovary ◽  
Meta Analysis ◽  
The United States ◽  
European Ancestry ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Ovary Syndrome ◽  
Northern European

Context: Genome-wide association studies (GWAS) have revealed new susceptibility loci for Chinese patients with polycystic ovary syndrome (PCOS). Because ethnic background adds to phenotypic diversities in PCOS, it seems plausible that genetic variants associated with PCOS act differently in various ethnic populations. Objective: We studied cross-ethnic effects of Chinese PCOS loci (ie, LHCGR, THADA, DENND1A, FSHR, c9orf3, YAP1, RAB5B/SUOX, HMGA2, TOX3, INSR, SUMO1P1) in patients of Northern European descent. Design: This study was a genetic association study conducted at an University Medical Center. Patients: Association was studied in 703 Dutch PCOS patients and 2164 Dutch controls. To assess the cross-ethnic effect, we performed a meta-analysis of the Dutch data combined with results of previously published studies in PCOS patients from China (n = 2254) and the United States (n = 2618). Adjusted for multiple testing, a P value <3.1 × 10−3 was considered statistically significant. Results: Meta-analysis of the Chinese, US, and Dutch data resulted in 12 significant variants mapping to the YAP1 (P value = 1.0× 10−9), RAB5B/SUOX (P value = 3.8 × 10−11), LHCGR (P value = 4.1 × 10−4), THADA (P value = 2.2 × 10−4 and P value = 1.3 × 10−3), DENND1A (P value = 2.3 × 10−3 and P value = 2.5 × 10−3), FSHR (P value = 3.8 × 10−5 and P value = 3.6 × 10−4), c9orf3 (P value = 2.0 × 10−6 and P value = 9.2 × 10−6), SUMO1P1 (P value = 2.3 × 10−3) loci with odds ratios ranging from 1.19 to 1.45 and 0.79 to 0.87. Conclusions: Overall, we observed for 12 of 17 genetic variants mapping to the Chinese PCOS loci similar effect size and identical direction in PCOS patients from Northern European ancestry, indicating a common genetic risk profile for PCOS across populations. Therefore, it is expected that large GWAS in PCOS patients from Northern European ancestry will partly identify similar loci as the GWAS in Chinese PCOS patients.

scholarly journals Non‐alcoholic fatty liver disease in premenopausal women with polycystic ovary syndrome: A systematic review and meta‐analysis

JGH Open ◽  
2021 ◽  
Vol 5 (4) ◽  
pp. 434-445
Author(s):  
Mohamed Shengir ◽  
Tianyan Chen ◽  
Elena Guadagno ◽  
Agnihotram V Ramanakumar ◽  
Peter Ghali ◽  
...  
Keyword(s):  
Systematic Review ◽  
Liver Disease ◽  
Polycystic Ovary Syndrome ◽  
Fatty Liver Disease ◽  
Polycystic Ovary ◽  
Meta Analysis ◽  
Premenopausal Women ◽  
Ovary Syndrome ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Effects of probiotic and synbiotic supplementation on insulin resistance in women with polycystic ovary syndrome: a meta-analysis

2021 ◽  
Vol 49 (7) ◽  
pp. 030006052110317
Author(s):  
Chenyun Miao ◽  
Qingge Guo ◽  
Xiaojie Fang ◽  
Yun Chen ◽  
Ying Zhao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Confidence Interval ◽  
Polycystic Ovary ◽  
Serum Insulin ◽  
Meta Analysis ◽  
Mean Difference ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Synbiotic Supplementation

Objective This meta-analysis evaluated the effect of probiotics and synbiotics on insulin resistance in patients with polycystic ovary syndrome (PCOS). Methods A systematic search was performed to identify all relevant publications listed on the electronic databases (PubMed®, Web of Science, Embase® and China National Knowledge Infrastructure) between inception and 30 October 2020. All statistical analyses were performed on randomized controlled trials (RCTs) using RevMan version 5.3 software provided by the Cochrane Collaboration. Results A total of 486 patients from seven RCTs were included in the meta-analysis. Probiotic and synbiotic supplementation appeared to improve levels of homeostatic model assessment of insulin resistance (mean difference = –0.37; 95% confidence interval –0.69, –0.05) and serum insulin (standardized mean difference = –0.66; 95% confidence interval –1.19, –0.12). The results failed to show any influence of probiotic and synbiotic supplementation on body mass index, waist circumference, hip circumference and fasting blood sugar. Conclusions Probiotics and synbiotics appear to have a partially beneficial effect on indices of insulin resistance in patients with PCOS.

scholarly journals Family-Based Quantitative Trait Meta-Analysis Implicates Rare Noncoding Variants in DENND1A in Polycystic Ovary Syndrome

2019 ◽  
Vol 104 (9) ◽  
pp. 3835-3850 ◽  
Author(s):  
Matthew Dapas ◽  
Ryan Sisk ◽  
Richard S Legro ◽  
Margrit Urbanek ◽  
Andrea Dunaif ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Quantitative Trait ◽  
Rare Variants ◽  
Polycystic Ovary ◽  
Association Studies ◽  
Meta Analysis ◽  
Premenopausal Women ◽  
Endocrine Disorders ◽  
Genome Wide Association Studies ◽  
Ovary Syndrome

AbstractContextPolycystic ovary syndrome (PCOS) is among the most common endocrine disorders of premenopausal women, affecting 5% to15% of this population depending on the diagnostic criteria applied. It is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. PCOS is highly heritable, but only a small proportion of this heritability can be accounted for by the common genetic susceptibility variants identified to date.ObjectiveThe objective of this study was to test whether rare genetic variants contribute to PCOS pathogenesis.Design, Patients, and MethodsWe performed whole-genome sequencing on DNA from 261 individuals from 62 families with one or more daughters with PCOS. We tested for associations of rare variants with PCOS and its concomitant hormonal traits using a quantitative trait meta-analysis.ResultsWe found rare variants in DENND1A (P = 5.31 × 10−5, adjusted P = 0.039) that were significantly associated with reproductive and metabolic traits in PCOS families.ConclusionsCommon variants in DENND1A have previously been associated with PCOS diagnosis in genome-wide association studies. Subsequent studies indicated that DENND1A is an important regulator of human ovarian androgen biosynthesis. Our findings provide additional evidence that DENND1A plays a central role in PCOS and suggest that rare noncoding variants contribute to disease pathogenesis.

scholarly journals Relationships Between Biochemical Markers of Hyperandrogenism and Metabolic Parameters in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 51 (01) ◽  
pp. 22-34 ◽  
Author(s):  
Mina Amiri ◽  
Fahimeh Tehrani ◽  
Razieh Bidhendi-Yarandi ◽  
Samira Behboudi-Gandevani ◽  
Fereidoun Azizi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Polycystic Ovary Syndrome ◽  
Biochemical Markers ◽  
Polycystic Ovary ◽  
Meta Analysis ◽  
Metabolic Parameters ◽  
High Density Lipoproteins ◽  
Total Testosterone ◽  
Ovary Syndrome ◽  
Increased Risk

AbstractWhile several studies have documented an increased risk of metabolic disorders in patients with polycystic ovary syndrome (PCOS), associations between androgenic and metabolic parameters in these patients are unclear. We aimed to investigate the relationships between biochemical markers of hyperandrogenism (HA) and metabolic parameters in women with PCOS. In this systematic review and meta-analysis, a literature search was performed in the PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science from 2000 to 2018 for assessing androgenic and metabolic parameters in PCOS patients. To assess the relationships between androgenic and metabolic parameters, meta-regression analysis was used. A total number of 33 studies involving 9905 patients with PCOS were included in this analysis. The associations of total testosterone (tT) with metabolic parameters were not significant; after adjustment for age and BMI, we detected associations of this androgen with low-density lipoproteins cholesterol (LDL-C) (β=0.006; 95% CI: 0.002, 0.01), high-density lipoproteins cholesterol (HDL-C) (β=–0.009; 95% CI: –0.02, –0.001), and systolic blood pressure (SBP) (β=–0.01; 95% CI: –0.03, –0.00). We observed a positive significant association between free testosterone (fT) and fasting insulin (β=0.49; 95% CI: 0.05, 0.91); this association remained significant after adjustment for confounders. We also detected a reverse association between fT and HDL-C (β=–0.41; 95% CI: –0.70, –0.12). There was a positive significant association between A4 and TG (β=0.02; 95% CI: 0.00, 0.04) after adjustment for PCOS diagnosis criteria. We also found significant negative associations between A4, TC, and LDL-C. Dehydroepiandrosterone sulfate (DHEAS) had a positive association with LDL-C (β=0.02; 95% CI: 0.001, 0.03) and a reverse significant association with HDL-C (β=–0.03; 95% CI: –0.06, –0.001). This meta-analysis confirmed the associations of some androgenic and metabolic parameters, indicating that measurement of these parameters may be useful for predicting metabolic risk in PCOS patients.

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