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 ◽  
...  

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.

Folia Medica ◽  
2013 ◽  
Vol 55 (2) ◽  
pp. 10-15 ◽  
Author(s):  
Dora D. Terzieva ◽  
Maria M. Orbetzova ◽  
Mitko D. Mitkov ◽  
Nonka G. Mateva

ABSTRACT There has been a surge of interest in recent years in studying the changes of serum melatonin concentrations in disorders that are associated with insulin resistance such as diabetes mellitus type 2 and polycystic ovary syndrome (PCOS). AIM: The present study was designed to investigate the day-time and night-time levels of serum melatonin and the cortisol rhythm in women with PCOS and compare them with those of healthy women. PATIENTS AND METHODS: This is a case-control study which included 30 women with PCOS and 25 healthy women. All hormonal measurements in both the study group and controls were carried out between days 3 and 5 counted from the beginning of the last regular menstrual cycle; they included serum levels of melatonin and cortisol at 03:00 a.m and 08:00 a.m, total testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone (LH), follicle stimulating hormone (FSH), and immunoreactive insulin at 08:00 a.m. RESULTS: Women with PCOS were found to have a significantly higher melatonin level at 08:00 a.m. and smaller mean night-day difference in the concentrations of melatonin in comparison with those of healthy women (natural log (Ln) night-day difference 0.60 ± 0.10 pg/ml versus 1.15 ± 0.14, p < 0.002). Melatonin to cortisol ratios at 03:00 a.m. and 08:00 a.m. showed no statistically significant differences between the two groups (Ln melatonin/ cortisol 03:00 a.m., 1.01 ± 0.06 versus 1.05 ± 0.05; Ln melatonin/cortisol at 08:00 a.m., 0.62 ± 0.01 versus 0.56 ± 0.03, p > 0.05). CONCLUSION: The results we obtained about the changes of melatonin in women with PCOS could help in elucidating the complex pathophysiological pattern of this disease.


Author(s):  
Dan Shan ◽  
Jinbiao Han ◽  
Yitong Cai ◽  
Li Zou ◽  
Liangzhi Xu ◽  
...  

Abstract Objective Polycystic ovary syndrome (PCOS) is a highly heritable disease. Emerging evidence elucidated the elevated prevalence of reproductive abnormalities in first-degree relatives (FDRs) of patients with PCOS. Methods Ten databases were searched in December 2020 (PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, CBM, CNKI, VIP and WanFang and WHO international clinical trials registry platform). This study included cohort, case–control, or cross-sectional studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement was followed. Dichotomous data from each of the eligible studies were combined by Mantel-Haenszel model. Standard mean differences with 95% confidence intervals were assessed. Heterogeneities were assessed using I  2 statistics, and the quality of evidence was evaluated by AHRQ EPC program and GRADE approach. Results Thirty-eight studies were included. The prevalence of PCOS (0.22; 95%CI 0.16 to 0.29), menstrual irregularities (0.28; 95%CI 0.22 to 0.34, P&lt;0.01) and ovary morphological changes were elevated in female PCOS FDRs. Female FDRs also presented with increased levels of luteinizing hormone, total testosterone (SMD, 0.53; 95%CI 0.28 to 0.78, P&lt;0.01), unconjugated testosterone, free androgen index, dehydroepiandrosterone sulfate (DHEAS), and anti-Mullerian hormone levels. Subgroup analyses indicated that some of these changes begun in pubertal girls. Furthermore, fathers of PCOS had higher risk of premature baldness. The DHEAS level was elevated in male FDRs. Conclusions The findings of this analysis suggested that FDRs of patients with PCOS suffered from reproductive endocrinological dysregulations. Thus, more attention should be focused on this population. (PROSPERO–CRD42020183243)


Author(s):  
Fatemeh Hesampour ◽  
Bahia Namavar Jahromi ◽  
Foroozan Tahmasebi ◽  
Behrouz Gharesi-Fard

Polycystic ovary syndrome (PCOS) is correlated with low-grade chronic inflammation. Interleukin-17A (IL-17A) and Interleukin-32 (IL-32) are two members of the pro-inflammatory cytokines which act as significant components of the immune system during certain inflammatory diseases. Along with immunological processes, genetic factors play major roles in predisposition to PCOS. There are myriad single nucleotide polymorphisms (SNPs) within IL-17A and IL-32 genes that may affect their production and the susceptibility of individuals to PCOS. The objective of the present research was to investigate the association between IL-17A (rs2275913) and IL-32 (rs9927163, rs4786370) SNPs, and also their serum levels with susceptibility to PCOS in a group of Iranian women. In this case-control study, 150 PCOS patients (mean age of 29.1 years) and 150 healthy women (mean age of 26.1 years) were analyzed in terms of IL-17A and IL-32 SNPs via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Furthermore, serum levels of IL-17A and IL-32 cytokines were measured through the use of ELISA method. There were significant differences between PCOS and healthy women regarding IL-17A rs2275913 alleles, genotypes frequencies (p=0.005, and 0.01, respectively) and the allelic distribution of IL-32 rs9927163 SNP (p=0.03). Additionally, significant differences were indicated between two groups concerning the AG genotype against AA+GG genotypes (p=0.009) and the GG genotype against AA+AG genotypes (p=0.006) in IL-17A rs2275913 SNP. In the matter of IL-32 gene SNPs, GC haplotype frequency was significantly different between patients and controls (p=0.05). Furthermore, IL-32 serum level was not significantly different between the two studied groups and the serum level of IL-17A was not detectable. In conclusion, IL-17A and IL-32 SNPs might be associated with predisposition to PCOS in Iranian women.


Author(s):  
Siyu Zhou ◽  
Danhua Lu ◽  
Shu Wen ◽  
Yongcheng Sheng ◽  
Deying Kang ◽  
...  

AbstractWe performed this updated systematic review and meta-analysis to evaluate anti-Müllerian hormone levels (AMH) in newborns of mothers with polycystic ovary syndrome (PCOS) compared with healthy controls. A search of the literature was conducted in the PubMed, MEDLINE, EMBASE, Cochrane Library, CBM, CNKI, WANFANG, and VIP for articles to assess AMH levels in offspring of PCOS and non-PCOS mothers irrespective of language. These databases were searched from their inception to December 7, 2020. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS) scoring system. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were adopted to calculate the overall estimates with random-effects models. A total of 6 studies with 846 participants were included. The pooled analysis found an increased AMH level in the umbilical cord blood in newborns of PCOS mothers (SMD =0.62, 95% CI [0.28, 0.95]). Subgroup analyses revealed an elevation of AMH concentrations in female neonates, neonates born to American and Asian PCOS mothers. In addition, higher AMH levels were also found in studies diagnosed by the National Institute of Health (NIH) criteria, maternal clinical/biochemical hyperandrogenism, or maternal body mass index (BMI) >30 kg/m2. Meta-regression analysis suggested that diagnostic criterion contributed mostly to the high heterogeneity. We demonstrated that AMH levels in neonates born to PCOS mothers were essentially higher, which indicates that AMH may act as an enigmatic role in the pathogenesis of PCOS which inhibits folliculogenesis in the fetal stage.


2007 ◽  
Vol 92 (7) ◽  
pp. 2659-2664 ◽  
Author(s):  
Mark O. Goodarzi ◽  
Heath J. Antoine ◽  
Ricardo Azziz

Abstract Context: The adrenal androgen (AA) metabolite dehydroepiandrosterone sulfate (DHEAS) is often elevated in women with polycystic ovary syndrome (PCOS); AA excess in PCOS appears to be, in part, a heritable trait. Dehydroepiandrosterone (DHEA) sulfonation is controlled by the enzymes DHEA sulfotransferase (SULT2A1) and steroid sulfatase (STS). Polymorphisms in these genes have not been evaluated as modulators of DHEAS level in PCOS. Objective: The aim was to test the hypothesis that variants in the SULT2A1 and STS genes are associated with DHEAS levels in women with PCOS. Design: Women with and without PCOS were genotyped for seven single nucleotide polymorphisms (SNPs) in SULT2A1 and seven SNPs in STS. SNPs and haplotypes were determined and tested for association with DHEAS. Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. Participants: A total of 287 white women with PCOS and 187 controls participated in the study. Main Measurements: SULT2A1 and STS genotype and DHEAS levels were measured. Results: In women with PCOS, SNP rs182420 in SULT2A1 was associated with DHEAS (P = 0.0035). Two haplotypes carrying the minor allele of rs182420 were also associated with DHEAS (P = 0.04 each). Variants within STS were not associated with DHEAS level. No associations were observed in control women. Conclusion: This study presents genetic evidence suggesting a potential role of SULT2A1, but not STS, in the inherited AA excess of PCOS.


Author(s):  
Rowaa Ahmed Mostafa ◽  
Mohmmed Mahmoud Al-Sherbeeny ◽  
Ibrahim Anwar Abdelazim ◽  
Amr Abdelaziz Khalifa ◽  
Ahmed Abdelkader Fahmy ◽  
...  

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