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目的探讨亚甲基四氢叶酸还原酶(methylenete-trahydrofolate reductase,MTHFR)基因多态性与2型糖尿病肾病(diabetic nephropathy,DN)的关系,为筛选DN高危人群及DN的早期干预治疗提供理论依据。方法采用以医院为基础的成组病例对照研究方法,于2009年6月至2010年1月对72例并发DN的2型糖尿病患者(病例组)和127例未并发DN的2型糖尿病患者(对照组)进行问卷调查、体格检查和实验室检查。应用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)技术进行MTHFR基因C677T多态性分析。结果病例组MTHFR基因TT基因型和T等位基因频率分别为30.6%和54.9%,均高于对照组(17.3%和42.1%),差异有统计学意义(P<0.05)。单因素logistic回归分析结果显示,MTHFR基因C677T多态性与DN之间存在统计学关联,其OR(95%CI)为1.673(1.100~2.545);携带MTHFR T等位基因的2型糖尿病患者发生DN的危险性是C等位基因携带者的1.670倍(95%CI:1.106~2.521),经过高血压、糖尿病病程和糖尿病家族史调整后,二者间的统计学关联仍然存在。结论 MTHFR基因C677T多态性与DN相关,T等位基因可增加2型糖尿病患者合并肾病的危险。
Objective To investigate the relationship between methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and type 2 diabetic nephropathy (DN), and to provide a theoretical basis for the early intervention treatment of DN high risk population and DN . Methods A group-based case-control study was conducted in 72 patients with type 2 diabetes mellitus (case group) and 127 type 2 diabetic patients without DN Control group) to conduct questionnaires, physical examination and laboratory tests. The MTHFR gene C677T polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results The frequencies of TT genotype and T allele of MTHFR gene in case group were 30.6% and 54.9%, respectively, which were significantly higher than those in control group (17.3% and 42.1%, respectively) (P <0.05). The result of univariate logistic regression analysis showed that the C677T polymorphism of MTHFR gene was associated with the DN, and the OR (95% CI) was 1.673 (1.100 ~ 2.545). Patients with type 2 diabetes carrying MTHFR T allele The risk of DN was 1.670-fold (95% CI: 1.106-2.521) among carriers of the C allele. After adjusting for hypertension, duration of diabetes and family history of diabetes, the statistical relationship between the two groups still existed. Conclusion The C677T polymorphism of MTHFR gene is associated with DN, and T allele may increase the risk of nephropathy in type 2 diabetic patients.