子痫前期中叶酸代谢酶基因多态性与同型半胱氨酸相关性研究

The relationship between folate metabolism enzyme gene polymorphism and homocysteine in preeclampsia

目的探讨四氢叶酸还原酶677、1298位点和甲硫氨酸合成酶还原酶66位点单核苷酸多态性及血浆同型半胱氨酸水平与子痫前期疾病发生的关系。方法分别收集150例子痫前期妇女和150例正常妊娠妇女口腔咽拭子,采用PCR-金磁微粒层析法检测基因多态性,同时采集受试者外周静脉血,ELISA法集中检测同型半胱氨酸水平。结果基因型频率的相对风险分析结果显示,MTHFR A1298C的CC基因型的发病风险是AA型的3.633倍,MTRR A66G的GG基因的发病风险是AA型的2.160倍,差异均有统计学意义(P<0.05);PE组Hcy浓度(10.53±6.17μmol/L),显著高于正常妊娠组,差异有统计学意义(P<0.01);基因多态性与Hcy水平的多元线性回归模型以及与PE疾病Logistic回归模型分析结果显示,MTRR A66G突变基因型GG与血浆Hcy浓度呈显著相关(P<0.01),且与子痫前期疾病的发生有主效应。结论 MTHFR基因A1298C位点的突变基因型CC和MTRR A66G位点的突变基因型GG是PE疾病的高风险因子,MTRR A66G位点基因多态性是影响子痫前期疾病血浆Hcy水平的重要遗传因素。

Objective： To investigate the the correlation of C677T and A1298C signle-nucleotide polymorphisms （SNPs） of the methylenetetrahydrofolate reductase （MTHFR） and A66G SNPs of methionine synthase reductase （MTRR） with plasma homocysteine levels in preeclampsia. Methods： 150 preeclampsia patients and 150 normal pregnancy subjects were included. The genotypes for the three SNPs in oropharyngeal swab were determined by PCR-gold magnetic particle chromatography, and at the same time, peripheral blood samples were collected the level of homocysteinea was detected by ELISA. Results： Analysis of genotype frequencies and relative risk showed that patients carrying MTHFR A1298C allele （OR=3.633, 95% CI.. 0.986-13.38, P〈0.05） or MTRR A66G allele （OR=2.160, 95% CI： 1.054-4.426, P〈0.05） were at increased risk of preeclampsia. The levels of Hcy in the PE group was （ 10.53 ± 6.17 ） mol/L, significantly higher than that in the normal pregnancy group. Multivariate linear model of gene polymorphism and the level of Hcy showed that MTRR A66G GG genotype was significantly correlated with the plasma concentration of Hcy （P〈0.01） , and the logistic regression analysis showed that they were the main risk factors and the occurrence of preeclampsia. Conclusion： The MTHFR A1298C CC genotype and MTRR A66G GG genotype is the high risk factor of PE, MTRR A66G gene polymorphism is an important determinant of plasma Hcy levels in preeclampsia.