Variant Alleles of the ESR1, PPARG, HMGA2, and MTHFR Genes Are Associated With Polycystic Ovary Syndrome Risk in a Chinese Population: A Case-Control Study

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age, with a prevalence of 6–8%. Although the etiology of PCOS has been investigated extensively, the association between genetic predisposition and PCOS risk is largely unknown. In this study, we genotyped 63 SNPs in 10 genes among 361 PCOS patients and 331 healthy controls in a Chinese Han population. The following variant alleles were significantly associated with decreased PCOS risk: ESR1 rs9340799 (P = 0.000), PPARG rs709154 (P = 0.013), and rs1151996 (P = 0.013), HMGA2 rs2272046 (P = 0.000), MTHFR rs1801133 (P = 0.000). Accordingly, the following genotypes at various loci were associated with reduced PCOS risk: GA genotype at rs9340799 (P < 0.0001) in ESR1, TA genotype at rs709154(P < 0.0001) in PPARG and CA genotype at rs2272046 (P < 0.0001) in HMGA2. Moreover, GA genotype at rs1999805 (P = 0.013) in ESR1 and TT genotype at rs1801133 in MTHFR (P < 0.0001) correlated with elevated PCOS risk. Furthermore, haplotype analysis revealed significant differences in haplotype distributions of CYP11A1, ESR2 and PPARG gene between cases and controls. In addition to confirming that ESR1 rs9340799, HMGA2 rs2272046 and MTHFR rs1801133 are related to the risk of PCOS, these findings also provide the first evidence that PPARG rs709154 and ESR1 rs1999805 are significantly associated with PCOS risk in a Chinese population. Further functional studies are warranted to elucidate the underlying biological mechanisms.

Identification of the Active Constituents and Significant Pathways of Cangfu Daotan Decoction for the Treatment of PCOS Based on Network Pharmacology

“…Research confirmed that PPARG rs709154 and ESR1 rs1999805 are significantly associated with PCOS risk in a Chinese population [37]. MMP9 may also be involved in the pathogenesis of PCOS [38].…”

PCOSKBR2: a database of genes, diseases, pathways, and networks associated with polycystic ovary syndrome

“…In a study by Zhao L et al, ESR1 polymorphisms were reported to be associated with hypertension and diabetes 28 . A case–control study by Jiao X et al, documented that altered expression of ESR1 can influence the risk of PCOS and its upregulation may contribute to abnormal follicular development 29 , 30 . Prostaglandin-endoperoxide synthase ( PTGS2) is a key enzyme for biosynthesis of the inflammatory hormone prostaglandin.…”

Association between methylenetetrahydrofolate reductase gene C677T polymorphism and susceptibility to polycystic ovary syndrome

“…Electronic database search yielded 161 studies, after applying strict inclusion and exclusion criteria total 23 articles were found suitable for the inclusion in the present meta-analysis.. Figure 1 shows the different phases of the study selection. Information was collected from 22 articles that associated MTHFR gene C677T polymorphism and PCOS (Glueck et al, 1999; Sills et al, 2001; Tsanadis et al, 2002; Lee et al, 2003; Orio et al, 2003; Palep-Singh et al, 2007; Choi et al, 2009; Bayram et al, 2010; Karadeniz et al, 2010; Idali et al, 2012; Jain et al 2012; Kazeerooni et al, 2013; Jiang et al, 2015; Naghavi et al, 2015; Qi et al, 2015; Carlus et al, 2016; Geng et al, 2016; Ozegowska et al, 2016; Sazafarowska et al, 2016 ; Wu et al, 2016; Jiao et al, 2018; Amuhtar and Amohaidi, 2019) (Table 1). In two studies, authors (Palep-Singh et al, 2007; Carlus et al, 2016) included two group of samples..…”

“…First of all, Glueck and colleagues (1999) have reported an association between MTHFR C677T polymorphism and PCOS. Since then, several reports are published regarding MTHFR C677T polymorphism as a risk factor for PCOS with positive (Wu et al, 2016; Jiao et al, 2018; Amuhtar and Amohaidi, 2019)as we as negative (Sills et al, 2001; Lee et al, 2003; Orio et al, 2003) results. Hence, the aim of the present study was to explore whether the MTHFR C677T polymorphism is associated with susceptibility to polycystic ovary syndrome (PCOS).…”