MTHFR、MTRR基因多态性与多囊卵巢综合征的相关性研究

目的探讨亚甲四氢叶酸还原酶(MTHFR)、甲硫氨酸合成酶还原酶(MTRR)基因多态性与多囊卵巢综合征(PCOS)的相关性。方法应用病例对照研究,收集2018年4月-2018年8月在广东省妇幼保健院就诊的育龄期PCOS患者55例为PCOS组,选取46例月经规则、有排卵,并完成一次生育的非PCOS患者作为对照组。在PCOS组中,按HOMA稳态模型(HOMA-IR)分为两组,PCOS胰岛素抵抗(PCOS-IR)组和PCOS非胰岛素抵抗(PCOS-NIR)组,按多毛评分标准(m FG score)和血清游离雄激素指数(FAI)分为两组,高雄激素症组和非高雄激素症组,分别提取血浆,利用荧光定量PCR方法检测MTHFR基因C677T、A1298C及MTRR基因A66G的单核苷酸多态性(SNPs),同时采用化学发光法检测两组血浆维生素B12、叶酸及同型半胱氨酸(HCY)的含量。结果MTHFR基因C677T等位基因C在PCOS组分布频率高于对照组,差异有统计学意义(P<0.05),等位基因C使PCOS的风险增加2.077倍(95%CI:1.132~3.812)。677CC基因型在PCOS组的分布频率明显高于对照组,差异有统计学意义(P<0.05),野生基因型(CC)与纯合突变基因型(TT)相比,患PCOS的风险提高了4.392倍(95%CI:1.005~19.196)。两组MTHFR基因A1298C、MTRR基因A66G各基因型和等位基因频率的分布差异无统计学意义(P>0.05)。在PCOS组中,PCOS-IR组和PCOS-NIR组以及高雄激素症组和非高雄激素症组在MTHFR基因C677T、A1298C及MTRR基因A66G各基因型分布差异无统计学意义(P>0.05),MTHFR C677T、A1298C及MTRR A66G位点分布之间不存在交互作用(P>0.05)。PCOS组中HCY水平较对照组明显升高,差异有统计学意义(P<0.05),两组血清维生素B12、叶酸水平差异均无统计学意义(均P>0.05)。结论MTHFR基因C677T多态性与PCOS的发病有一定的相关性,CC基因型可增加PCOS的发生风险,但与胰岛素抵抗(IR)和高雄激素症的发生风险无关。MTHFR基因A1298C、MTRRA66G各基因型与PCOS的发生、IR及高雄激素症的发生无关,PCOS组HCY偏高。

The study of the folate metabolism related gene polymorphisms of MTHFR and MTRR with polycystic ovary syndrome

Objective To explore the association between methylenetetrahydrofolate reductase(MTHFR)C677 T,A1298 C and methionine synthase reductase(MTRR)A66 G genes and polycystic ovary syndrome(PCOS).Methods case control study was used to collect 55 PCOS patients of reproductive age who were treated in Guangdong Provincial Maternal and Child Health Hospital from April 2018 to August 2018 as the PCOS group.46 non-PCOS patients with regular menstrual cycles,normal livebird were selected as control group.PCOS pations were divided into two groups:the PCOS insulin resistance(PCOS-IR)group and the PCOS without insulin resistance(PCOSNIR)group according to the homeostasis model assessment(HOMA-IR).The PCOS patients were divided into two groups:the high androgen group and the non-androgen group according to the multi-hair score standard(m F-G score)and serum free androgen index(FAI).Blood samples were extracted and the single nucleotide polymorphisms(SNPs)of MTHFR genes C677 T,A1298 C,and MTRR gene A66 G were detected by fluorescent quantitative PCR.The chemiluminescence method was used to detect the levels of plasma vitamin B12,folate and homocysteine(HCY)in the two groups.Results The distribution frequency of MTHFR gene C677 T allele C in the PCOS group was higher than that in the control group(P<0.05).Allele C increased the risk for PCOS by 2.077 times(95%CI:1.132~3.812).The distribution frequency of 677 CC genotype in the PCOS group was significantly higher than that in the control group(P<0.05).Compared with the homozygous mutation genotype(TT),the wild genotype(CC)was more common with an OR of 4.392(95%CI:1.005~19.196)among PCOS cases than controls.There was no significant difference in the distribution of genotypes and allele frequencies of MTHFR gene A1298 C and MTRR gene A66 G between the two groups(P>0.05).In the PCOS group,there was no significant difference in the distribution of genotypes in the MTHFR gene C677 T,A1298 C,and MTRR gene A66 G between the PCOS-IR group and the PCOS-NIR group,and between the high androgen group and the non-androgen group(P>0.05).There was no interaction between MTHFR C677 T,A1298 C,and MTRR A66 G loci(P>0.05).The HCY level in the PCOS group was significantly higher than that in the control group(P<0.05.There was no significant difference in serum vitamin B12 and folate levels between the two groups(all P>0.05).Conclusion MTHFR gene C677 T polymorphism is associated with PCOS,for which CC genotype can increase the risk of PCOS,but is not associated with the risk of insulin resistance and hyperandrogenism.The A1298 C polymorphism of MTHFR gene and A66 G polymorphism of MTRR gene are not associated with the occurrence of PCOS,insulin resistance,and hyperandrogens,The serum HCY level of PCOS group is higher.