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

ABSTRACT Objective 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). Subjects and methods 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). Results 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). Conclusion 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.

摘要（ABSTRACT）
研究目的：探讨叶酸代谢相关基因（MTHFR C677T、MTHFR A1298C、MTR A2756G、MTRR A66G及RFC-1 A80G）的遗传变异与多囊卵巢综合征（Polycystic Ovary Syndrome, PCOS）发生发展的关联。
研究对象与方法：本研究纳入203名女性受试者，其中多囊卵巢综合征患者99例，健康对照104例。采用聚合酶链反应-限制性片段长度多态性（Polymerase Chain Reaction-Restriction Fragment Length Polymorphism, PCR-RFLP）技术完成基因分型。统计学分析采用卡方检验及多元logistic回归分析，单倍型分析通过SNPstat程序进行。结果以比值比（Odds Ratio, OR）及95%置信区间（95% Confidence Interval, CI-95%）呈现，检验水准设定为5%（p ≤ 0.05）。
研究结果：RFC-1 A80G多态性的基因型分布在两组间存在显著差异，其中杂合基因型（AG基因型）在对照组中最为常见。MTRR A66G多态性的纯合突变基因型（GG基因型）在对照组中占比最高。MTHFR C677T与A1298C多态性构成的T-C单倍型在对照组中更为频发（OR=0.19；95%CI：0.04~0.93，p=0.042）。多因素分析显示，多囊卵巢综合征家族史在病例组中更为普遍（OR=3.29；95%CI：1.48~7.31；p=0.003）。
研究结论：在本研究病例队列中，MTRR A66G多态性的纯合突变基因型、RFC-1 A80G多态性的杂合基因型，以及MTHFR基因C677T与A1298C多态性构成的T-C单倍型，可能作为该疾病的保护性遗传因素。