亚甲基四氢叶酸还原酶基因多态性与糖尿病合并冠心病的相关性

目的:研究亚甲基四氢叶酸还原酶(MTHFR)基因多态性及血浆同型半胱氨酸水平与2型糖尿病患者合并冠心病的关系。方法:运用多聚酶链反应-限制性内切酶片段长度多态性技术(PCR-RFLP)检测228例2型糖尿病患者(其中126例伴冠心病)及114例正常对照组MTHFRC677T基因型,采用高效液相色谱法测定血浆同型半胱氨酸水平。结果:在114例正常对照组中突变T等位基因频率为38.0%,与中国香港地区人群T等位基因频率(33.0%)相似。糖尿病组MTHFR基因型频率分布与正常对照组相比差异无统计学意义(χ2=3.67,P>0.05)。糖尿病伴冠心病组MTHFRT等位基因频率(45.2%)明显高于糖尿病不伴冠心病组(30.4%),基因型和等位基因频率分布差异均有统计学意义(分别为χ2=11.98,P<0.01;χ2=8.72,P<0.01),T等位基因与糖尿病并发冠心病密切相关(OR=1.89,95%CI:1.24-2.88))。糖尿病伴冠心病组、糖尿病不伴冠心病组及正常对照组中,MTH-FR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升高可能是糖尿病并发冠心病的重要遗传因素。

Methylenetetrahydrofolate Reductase Polymorphism Associates with Susceptibility to Coronary Heart Disease in Chinese Type 2 Diabetic Patients

Objective:To investigate the distribution of methylenetetrahydrofolate reductase (MTHFR) genotypes in Chinese population and the association between the C677T variant of MTHFR gene and coronary heart disease (CHD) in Chinese type 2 diabetic patients. Methods: A total of 228 unrelated patients with type 2 diabetes mellitus (126 with coronary heart disease) and 114 healthy control subjects were involved in this study. The MTHFR genotypes were analyzed by PCR followed by HinfⅠ digestion. Plasma total homocysteine levels were measured using high-performance liquid chromatography (HPLC) with fluorescence detection. Results: In 114 healthy control subjects, the frequency of the mutant T allele was 38.0%, which is similar to that of population from Chinese Hong Kong. The genotypes distribution was not different between control subjects and type 2 diabetic patients (χ2=3.67, P>0.05). Genotypic analysis revealed that type 2 diabetic patients with CHD displayed a greater prevalence of T allele (45.2%) than type 2 diabetic patients without CHD (30.4%) did (χ2=8.72, P<0.01). The odds ratio for CHD in type 2 diabetic patients in presence of T allele was 1.89 (CI 95%: 1.24-2.88). The MTHFR genotype were different between diabetic patients with and without CHD (χ2 =11.98, P<0.01). Moreover, plasma homocysteine levels were markedly higher in individuals with TT genotype than those with CC or CT genotypes or CC plus CT genotypes. Conclusion: The C677T mutation of MTHFR gene is common in Chinese population. MTHFR C677T gene polymorphism associated with a predisposition to increased plasma homocysteine levels might be a useful predictive marker for CHD in Chinese type 2 diabetic patients.