MTHFR基因多态性与2型糖尿病肾病相关性的研究

Reserch on the association between MTHFR（methylentetrahydrofolate） reductase gene polymorphism and type 2 diabetic nephropathy（DN）

目的 研究亚甲基四氢叶酸还原酶（MTHFR）基因多态性与2型糖尿病肾病（DN）易感性的关系.方法 选择111例山西地区汉族人2型糖尿病患者,其中糖尿病肾病（DN＋）组56例,糖尿病非肾病（DN-）组55例,运用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）技术并结合琼脂糖凝胶电泳的方法检测111例患者的MTHFR基因多态性,测定各组间基因型频率和等位基因频率.结果 纯合基因型TT、T等位基因在DN＋组（21.43％,46.43％）的频率均明显高于DN-组（7.27％,29.09％）,差异均具有统计学意义（P＜0.05）.无论是在DN＋组还是DN-组中,TT基因型患者血同型半胱氨酸（Hcy）平均水平均大于CC基因型和CT基因型患者,DN＋组血浆Hcy水平明显高于DN-组,差异均具有统计学意义（P＜0.05）.在叶酸浓度≤6.92nmol/L时,DN＋组（24.24％,48.49％） TT型发生率及T等位基因频率明显高于DN-组（3.70％,25.93％）（P＜0.05）,当叶酸浓度＞6,92nmol/L时,DN＋组TT型发生率及T等位基因频率与DN-组无差异（P＞0.05）.结论 MTHFR基因C677T多态性与糖尿病肾病（DN）发生具有相关性,突变的T等位基因是DN易感基因,但其影响效果受叶酸浓度的影响.

Objectives To investigate the association between MTHFR gene polymorphism and the susceptibility to DN in type 2 diabetes mellitus.Methods 120 type 2 diabetes mellitus in the Shanxi Han Chinese,60 with type 2 diabetic nephropathy（DN ＋）,60 without nephropathy but type 2 diabetes（DN-）,were selected to join in the study.The polymorphism of MTHFR was assayed by PCR-RFLP and agarose gel electrophoresis method,and then allele frequencies and genotype frequencies statistically computed.Results The frequency of MTHFR TT homogenetic type and CT heterogenetic type and allele Twas significant higher in DN（＋） （21.43%,46.43%）than DN（-） （7.27%,29.09%）,and the differences was significantly（P 〈0.05）.No matter in group DN（＋） or DN （-） group,the TT genotype average level of Hcy was greater than the CC genotype and CT genotype.Plasma level of Hcy in DN（＋） was significantly higher than that in DN（-）,and the differences was significantly.In subject with serum folate ≤6.92,the frequency genotype TT and frequency T of DN （＋） （24.24%,48.49%） was higher than that of DN （-） （3.70%,25.93 %） （P 〈 0.05）.Among subject with serum folate 〉 6.92,genotype and allele distribution was not different from the DN （-） （P 〉 0.05）.Conclusions In type 2 DM of Han nationality in Shanxi China,MTHFR gene C677T mutation was associated with diabetic nephropathy,and the allele T might be a susceptible gene of diabetic nephropathy.But influenced by folate concentration.