孕早期妇女MTHFR和MTRR基因多态性分布特征及与Hcy浓度之间的相关性

Correlation between MTHFR and MTRR gene polymorphism and Hcy concentration in early pregnant women

目的了解深圳地区孕早期妇女5,10-亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)C677T,A1298C及甲硫氨酸合成酶还原酶(methionine synthase reductase,MTRR)A66G位点基因多态性分布特征及其多态性与血浆同型半胱氨酸(Homocysteine,Hcy)浓度的相关性,为孕早期妇女补充叶酸提供理论依据。方法选择2016年3月~2017年8月来医院进行产检的孕早期妇女620例,采用多重荧光PCR法分析MTHFR的C677T,A1298C和MTRR的A66G基因位点的多态性,同时采用Backman AU400全血动生化分析仪检测孕妇血清中Hcy浓度,并分析基因多态性与Hcy浓度之间的相关性。结果 MTHFR基因C677T位点以CC型为主,检出率为54.03%,明显高于CT型的32.58%和TT型的13.39%,差异有统计学意义(χ2=4.182,5.623,P<0.05),A1298C位点以AA型为主,检出率为70.65%,明显高于AC型的19.68%和CC型的9.68%,差异有统计学意义(χ2=8.952,11.351,P<0.05);MTRR基因A66G位点以AG型为主,检出率为61.13%,明显高于AA型的34.52%和GG型的4.35%,差异有统计学意义(χ2=5.875,7.501,P<0.05)。MTHFR基因C677T位点等位基因C和T检出率分别为58.55%和41.45%,A1298C位点等位基因A和C检出率分别为占72.58%和27.42%;MTRR基因A66G位点等位基因A和G检出率分别为63.55%和36.45%。MTHFR基因C677T位点TT型Hcy浓度为12.59±2.14μmol/L,明显高于CC型和CT型,差异有统计学意义(t=3.264,3.715,P<0.05),A1298C位点CC型Hcy浓度为9.76±1.83μmol/L,明显高于AA型和AC型,差异有统计学意义(t=3.845,4.032,P<0.05);MTRR基因A66G位点AG型Hcy浓度为11.04±1.97μmol/L,明显高于AA型和与GG型,差异有统计学意义(t=3.292,4.166,P<0.05)。结论深圳地区孕早期妇女MTHFR C677T,A1298C和MTRR A66G基因多态性频率与别的地区存在差异,具有地区特异性。MTHFR基因C677T位点TT,A1298C位点CC及MTRR基因A66G位点AG突变基因携带者血清Hcy浓度均明显高于其它突变基因携带者。

Objective：To understand the early pregnant women in shenzhen area 5,10-methylene tetrahydrofolate reductase（MTHFR）C677T,A1298C and methionine synthase reductase（MTRR）A66G loci gene polymorphism distribution characteristics and its polymorphism and plasma concentration of Homocysteine（Homocysteine,Hcy）,as to provide theoretical basis for early pregnant women folic acid supplementation. Methods：Selection in March 2016 to August 2017 to shenzhen area hospitals for prenatal early pregnancy women 620 cases,using multiple fluorescent PCR method to analysis the MTHFR C677T,A1298C and MTRR A66G polymorphic loci,at the same time with Backman AU400 whole blood biochemical analyzer to detect serum Hcy concentration in pregnant women,and analyze the correlation between gene polymorphism and Hcy concentration. Results：The mainly of MTHFR gene C677T site was CC type.,detection rate was 54.03%,significantly higher than CT type 32.58% and TT type 13.39%,difference was statistically significant（χ2=4.182,5.623,P〈0.05）,the mainly of A1298C site was AA type,detection rate was 70.65%,significantly higher than the AC type19.68% and CC type 9.68%,the difference was statistically significant（χ2=8.952,11.351,P〈0.05）;The mainly of MTRR A66G site gene was AG type,the detection rate was 61.13%,which was significantly higher than that of the AA type 34.52% and GG type 4.35%,the difference was statistically significant（χ2=5.875,7.501,P〈0.05）. The detection rates of alleles C and T at the MTHFR gene C677T site were 58.55% and 41.45%,respectively. The detection rate of A1298C site alleles A and C were 72.58% and 27.42% respectively. The detection rate of alleles A and G in the MTRR gene A66G were 63.55% and 36.45%,respectively. MTHFR gene C677T site TT type Hcy concentration was 12.59±2.14 μmol/L,significantly higher than the CC and CT,the difference was statistically significant（t=3.264,3.715,P〈0.05）,A1298C site CC type Hcy concentration was 9.76±1.83 μmol/L,significantly higher than that of AA type and AC type,was statistically significant difference（t=3.845,4.032,P〈0.05）;The AG type of the MTRR gene A66G Hcy concentration was 11.04±1.97μmol/L,significantly higher than that of AA and GG,and the difference was statistically significant（t=3.292,4.166,P〈0.05）. Conclusion：The polymorphic frequencies of MTHFR C677T,A1298C and MTRR A66G in the early pregnant women in shenzhen area were different from those in other regions and had regional specificity. the serum Hcy concentration of the patients with the MTHFR gene C677T site TT,A1298C site CC and the MTRR gene A66G site AG was significantly higher than that of other mutated gene carriers.