亚甲基四氢叶酸还原酶基因多态性与糖尿病肾病相关性研究

目的：研究亚甲基四氢叶酸还原酶（MTHFR）基因多态性与2型糖尿病肾病的关系。方法：运用聚合酶链反应－限制性片段长度多态性技术（PCR－RFLP）检测85例2型糖尿病患者（其中39例伴糖尿病肾病）及57例正常对照组MTHFR C677T基因型，采用高效液相色谱法测定血浆同型半胱酸水平。结果：糖尿病肾病组MTHFR基因TT纯合基因型，CT杂合基因型及T等位基因频率（分别为38．21％，51．28％，53．85％）均明显高于糖尿病不伴肾病组（分别为19．57％，28．26％，33．70％）及正常对照组（分别为17．54％，28．07％，31．58），基因型和等位基因频率分布差异均有统计学意义（P＜0．05），而MTHFR基因该多态性在不伴肾病组与正常对照组之间差异无显著性（P＞0．05），T等位基因与糖尿病肾病的发生密切相关（OR＝2．30，95％可信区间；1．24－4．26）。糖尿病肾病组，糖尿病不伴肾病组及正常对照组中，MTHFR基因有C677T突变者血浆同型半胱氨酸水平均显著高于无基因突变者。结论：MTHFR基因C677T位碱基突变致血浆同型半胱氨酸水平高是糖尿病肾病发病的重要遗传因素。

The association of methylenetetrahydrofolate reductase gene polymorphism with nephropathy in type 2 diabetes mellitus in Chinese

OBJECTIVE: To evaluate the role of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in Chinese patients with type 2 diabetes mellitus and diabetic nephropathy(DN). METHODS: 85 type 2 diabetes mellitus patients and 57 controls were recruited in the study. MTHFR genetic C677T polymorphism was determined with PCR-restriction fragment length polymorphisms (RFLP). Plasma total homocysteine level was measured using high-performance liquid chromatography (HPLC) with fluorescence detection. RESULTS: The frequency of MTHFR TT homogenetic type and CT heterogenetic type and allele T(28.21%, 51.28%, 53.85%) was significantly higher in type 2 diabetes mellitus with diabetic nephropathy group than those without nephropathy (19.57%, 28.26%, 33.70%) or normal controls (17.54%, 28.07%, 31.58%). However, there was no significant difference of MTHFR genotype and allele frequency between type 2 diabetes mellitus without nephropathy and normal controls. The presence of T allele appeared to have a stronger association with the development of diabetic nephropathy. The odds ratio was 2.30 and the 95% confidence interval was 1.24-4.26. Moreover, plasma homocysteine levels were markedly higher in patients with TT or CT genotype than those in patients with CC genotype. CONCLUSIONS: MTHFR gene C677T mutation associated with a predisposition to increased plasma homocysteine levels may represent a genetic risk factor for diabetic nephropathy in Chinese type 2 diabetes mellitus.