Can the genetic polymorphisms of the folate metabolism have an influence in the polycystic ovary syndrome?

Tayssia Beatriz Dos Santos,Marly Aparecida Spadotto Balarin,Roseane Lopes Silva-Grecco,Marco Fábio Prata Lima,Mariangela Torreglosa Ruiz Cintra,Elisabete Aparecida Mantovani Rodrigues De Resende,Helena Korres De Paula,Mariana Kefalas Oliveira Gomes

doi:10.20945/2359-3997000000167

Tayssia Beatriz Dos Santos, Marly Aparecida Spadotto Balarin + Show 6 more

Open Access

https://doi.org/10.20945/2359-3997000000167

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Abstract

To investigate the association of the genetic variants of the folate metabolism genes (MTHFR C677T; MTHFR A1298C; MTR A2756G; MTRR A66G and RFC-1 A80G) with the development of polycystic ovary syndrome (PCOS). This study included 203 women (99 women with PCOS and 104 controls). The genotyping was performed by PCR-RFLP. Chi-squared test and multiple logistic regression were used in the statistical analysis. Haplotype analysis was conducted using the SNPstat program. The results were presented in odds ratio (OR) and confidence interval of 95% (CI-95%), with a significance level of 5% (p ≤ 0.05). The genotypic distribution of the RFC-1 A80G polymorphism showed significant difference between the two groups, showing that the heterozygous genotype (AG genotype) was most frequent in controls. The polymorphic homozygous (GG genotype) of MTRR A66G polymorphism were most frequent in controls. The T-C haplotype MTHFR C677T and A1298C polymorphisms were more frequent in the control group (OR = 0.19; CI 95% - 0.04 to 0.93 e p = 0.042). The multivariate analysis evidenced that family history of PCOS was more frequent in the PCOS group (OR = 3.29; CI 95% - 1.48 to 7.31; p = 0.003). In our casuistry, the polymorphic homozygous of MTRR A66G polymorphism gene and heterozygous of RFC-1 A80G polymorphism gene, the haplotype T-C C677T and A1298C polymorphisms of MTHFR gene, can be associated with protective factors for the disease.

Highlights

The Polycystic Ovary Syndrome (PCOS) is characterized by the presence of polycystic ovaries morphology, oligo or chronic anovulation and hyperandrogenism [1,2].The etiology of PCOS is unclear, but this syndrome is a multifactorial disease that results from complex interactions between genetic and environmental factors [3]
This study evaluated the association of five genetic polymorphisms involved in the folate metabolism (MTHFR C677T, methylenetetrahydrofolate reductase (MTHFR) A1298C, MTR A2756G, MTRR A66G and reduced folate carrier 1 (RFC-1) A80G) in women with PCOS and controls in a Brazilian population
The polymorphisms MTHFR A1298C were in disequilibrium in the cases and controls, and the polymorphisms MTRR A66G and RCF-1 A80G presented disequilibrium in the case group

Summary

Introduction

The Polycystic Ovary Syndrome (PCOS) is characterized by the presence of polycystic ovaries morphology, oligo or chronic anovulation and hyperandrogenism [1,2].The etiology of PCOS is unclear, but this syndrome is a multifactorial disease that results from complex interactions between genetic and environmental factors [3]. The Polycystic Ovary Syndrome (PCOS) is characterized by the presence of polycystic ovaries morphology, oligo or chronic anovulation and hyperandrogenism [1,2]. One study performed in 1968 showed the possible effect of folic acid on ovarian function in rats, evidencing that a deficiency or an excess of folic acid partially inhibited ovulation [4]. The effect of folate deficiency was studied on the cytomorphology and the kinetics of proliferation of ovarian granulosa cells, and the epithelial cells lining the uterus, cervix and vagina of six sexually mature female rhesus monkey and showed degeneration of Graffian follicles with an increase in atretic and cystic follicles, accompanied by. Folate polymorphisms PCOS a depletion of granulosa cells and reduction or even absence of corpora lutea [5]. Several studies confirmed the presence of increased serum Hcy concentration in PCOS patients [7]

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