2型糖尿病肾病患者p22phox基因多态性的研究

目的研究NADPH氧化酶p22phox亚基基因多态性与中国上海汉族人群2型糖尿病肾病（DN）相关性。方法应用限制性片断长度多态性（RFLP）-PCR方法对105例健康对照组和194例2型糖尿病（DM）患者（其中71例DN）进行p22phox亚基C242T、A640G基因型检测。同时检测其身高、体重、血压、血脂、空腹血糖及胰岛素、HbAlc的水平。结果DN组CT＋TT基因型频率明显高于2型DM和对照组（26．76％比17．07％、3．81％，P=0．0002）；DN组T等位基因频率明显高于2型DM和对照组（22．54％比13．42％、2．86％，P=0．0001）；3组间AA基因型频率与A等位基因频率差异无统计学意义。多元回归分析显示，T242等位基因、收缩压、空腹血糖、HbAlc、β细胞功能指数（Homa-IS）是DN的危险因素。结论p22phox亚基T242等位基因变异可能是中国上海地区汉族人群DN的易感基因：而p22phox亚基A640G基因多态性与上述人群DN无相关性。T242等位基因、收缩压、空腹血糖、HbAlc、Homa-IS是DN的危险因素。

Association between NADPH oxidase subunit p22phox gene polymorphism and type 2 diabetic nephropathy patients in Shanghai

Objective To evaluate the association between the C242T and A640G polymorphism in the p22phox gene, an essential component of NADPH oxidase, and type 2 diabetic nephropathy patients in Shanghai. Methods C242T and A640G polymorphism of the p22phox gene were detected by polymerase chain reaction-restriction fragment-length polymorphism in 194 type 2 diabetic patients, including 71 diabetic nephropathy, and 105 healthy subjects. Meanwhile the fast blood glucose, fast blood insulin, blood pressure, TG, TC, HDL, LDL, HbA1c and body mass index were examined. Results The frequency of CT+TT genotype in diabetic nephropathy patients was significantly higher than that in type 2 diabetic subjects and healthy subjects (26.76% vs. 17.07%,3.81%,P=0.0002); and so was the T allele genotype (22.54% vs. 13.42%,2.86%,P=0.0001). There were no differences of the AG+AA genotypes or A allele genotypes among three groups (P > 0.05). Logistic multiple regression analysis showed T242 allele, body mass index, fasting blood glucose, HbAlc, Homa-IS, systolic blood pressure were risk factors of type 2 diabetic nephropathy. Conclusions p22phox C242T gene polymorphism is associated with diabetic nephropathy in Shanghai people. p22phox subunit T allele mutation is pnobabaly one of predisposing genes of type 2 diabetic nephropathy, and p22phox A640G gene polymorphism is not associated with diabetic nephropathy in Shanghai people. T242 allele, fasting blood glucose, HbAlc, Homa-IS, systolic blood pressure are risk factors of type 2 diabetic nephropathy.