临沂市汉族女性MTHFR和MTRR基因多态性分布及其与同型半胱氨酸水平的相关性

Methylenetetrahydrofolate reductase and methionine synthase reductase gene polymorphisms in ethnic Han women from Linyi

目的分析山东省临沂市汉族女性亚甲基四氢叶酸还原酶（methylenetetrahydrofolatereductase，MTHFR）677C／T、1298A／C及甲硫氨酸合成酶还原酶（methioninesynthasereductase，MTRR）66A／G基因多态性的分布特征，及其与同型半胱氨酸（homocysteine，Hcy）水平的相关性。方法采用横断面调查研究方法，以临沂市825名汉族女性为研究对象，采集口腔黏膜上皮细胞，提取基因组DNA，采用Taqman-MGB技术进行MTHFR和MTRR基因多态性检测。统计分析基因多态性的分布特征，并与其他地区（山东省潍坊市、河南省郑州市、四川省德阳市及海南省）的数据进行比较。采用酶转换法检测281名研究对象的血浆Hcy浓度，根据MTHFR基因多态性将其分为MTHFR酶活性基本正常组和显著降低组，分析Hcy水平与MTHFR酶活性的相关性。结果（1）临沂市汉族女性的MTHFR677CC、CT、TT的基因型频率分别为16．7％、48．3％和35．0％，TT纯合突变高于四川德阳和海南地区（P〈0．01）。MTHFR1298AA、AC、CC的基因型频率分别为76．0％、21．6％和2．4％，CC纯合突变基因型频率低于四川德阳和海南地区（P〈0．01）。MTRR66AA、AG、GG的基因型频率分别为54．7％、39．4％和5．9％，GG纯合突变基因型频率低于海南地区（P〈0．01）。（2）MTHFR酶活性显著降低组的Hcy水平高于酶活性基本正常组，差异有统计学意义（P〈O．05）。结论（1）临沂市汉族女性有不同于其他地区的M丁HFR和MTRR基因多态性分布特征。（2）MTHFR基因多态性导致的酶活性降低是Hcy水平升高的风险因素。

Objective To explore the distribution of genetic polymorphisms of methylenetetrahydrofolate reductase （MTHFR） 677C/T, 1298A/C and methionine synthase reductase （MTRR） 66A/G among ethnic Han females from Linyi, and to correlate it with serum level of homocysteine （Hey）. Methods A cross-sectional study was carried out. Oral epithelial cell samples were collected from 825 subjects. MTHFR and MTRR gene polymorphisms were determined with a Taqman-Minor Groove Binder （MGB） method. Distribution of gene polymorphisms was analyzed and compared with others regions of China including Weifang, Zhengzhou, Deyang and Hainan. A biochemical assay was also carried out to determine the total Hcy in plasma of 281 subjects. The reductase activity of MTHFR was classified into decreased and stable groups according to genetic polymorphism of MTHFR. Correlation between MTHFR groups and total Hcy level were also explored. Results （1） The frequencies of MTHFR 677CC, CT and TT genotypes of the selected subjects were 16.7%, 48.3% and 35.0%, respectively. The frequencies of MTHFR 1298AA, AC and CC genotypes were 76.0%, 21. 6%and 2.4%, respectively. And those of MTRR 66AA, AG and GG genotypes were 54. 7%, 39. 4% and 5. 9%, respectively. For the selected subjects, their frequency of MTHFR 677TT genotype was higher than that of Deyang and Hainan （P〈 0.01）, whilst the frequency of MTHFR 1298CC genotype was lower than that of Deyang and Hainan （P〈0.01）, and the frequency of MTRR 66 GG genotype was lower than that of Hainan （P〈0.01）. （2）The Hcy level for those with decreased MTHFR activity was significantly higher than those with stable MTHFR activity （P〈0. 05）. Conclusion MTHFR gene 677C/T, 1298A/C and MTRR 66A/G polymorphisms in ethnic Han women from Linyi have differed significantly from other regions of China. Decreased MTHFR activity caused by genetic polymorphisms is a risk factor for raised Hcy level.