Role of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in polycystic ovary syndrome risk

Abstract

Polycystic ovary syndrome is one of the most frequently encountered endocrine malfunctions. Methylenetetrahydrofolate reductase (MTHFR) plays a vital role in folate metabolism, DNA methylation, and RNA synthesis. We carried out a study to investigate the association between MTHFR C677T and A1298C genetic variations and the risk of polycystic ovary syndrome in a Chinese population. We recruited 244 patients and 257 control subjects from an Inner Mongolian Medical University to this hospital-based, case-control study. The genotyping of the MTHFR C677T and A1298C polymorphisms was carried out using polymerase chain reaction coupled with restriction fragment length polymorphism. Using multiple logistic regression analysis, we found that the TT genotype and the T allele of MTHFR C677T carriers showed increased risk of polycystic ovary syndrome compared with the wild-type genotype or allele carriers. The adjusted ORs for the TT genotype and the T allele of MTHFR C677T were 1.84 (1.05-3.26) and 1.38 (1.06-1.81), respectively. Subjects carrying the CC genotype (OR = 3.98, 95%CI = 1.60-11.23) and the C allele (OR = 1.46, 95%CI = 1.07-2.00) of MTHFR A1298C had an elevated risk of polycystic ovary syndrome compared with the AA genotype and A allele carriers. In conclusion, our study suggests that the MTHFR C677T and A1298C polymorphisms may have contributed to the risk of polycystic ovary syndrome in the Chinese women investigated. Further research involving a greater number of individuals is warranted to confirm our results.

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).…”

Polycystic Ovary Syndrome: Pathophysiology, Presentation and Treatment a Mini-Review Article

“…One theory maintains that underlying insulin resistance exacerbates hyperandrogenism by suppressing synthesis of sex hormone-binding globulin and increasing adrenal and ovarian synthesis of androgens, thereby increasing androgen levels. These androgens then lead to irregular menses and physical manifestations of hyperandrogenism (9,(12)(13)(14)(15).…”

“…Key features of the syndrome include altered gonadotropin secretion, hyperandrogenism, and insulin resistance. Women with PCOS have an increased pulse frequency of the gonadotropin luteinizing hormone (LH) (11)(12)(13)(14)(15). It is uncertain whether increased LH release is due to an inherent defect in the pulsatile release of gonadotropin-releasing hormone (Gn-RH) from the hypothalamus or to low levels of circulating progestin, as lower levels of progestin may be associated with accelerated Gn-RH pulsatility.…”

“…Regardless of the source, increased pulsatility of Gn-RH favors the production of LH over follicle-stimulating hormone (FSH) and results in relatively higher circulating levels of LH. The effect of higher concentrations of LH is increased production of androgens by ovarian theca cells (15,16).…”