【摘要】 目的　探讨染色体 7q35区的醛糖还原酶(AR)和内皮细胞型一氧化氮合酶 (eNOS)基因多态性与中国北方汉族人 2型糖尿病肾病(DN)之间的关系。方法　采用PCR RFLP技术,检测AR基因启动子区C( -106)T点突变和eNOS基因第 7外显子G894T点突变;采用琼脂糖凝胶直接电泳PCR产物,检测eNOS基因第 4内含子 27bp的插入 /缺失(4a/4b)多态,分析 134例 2型糖尿病组(包括 70例DN+组和64例DN-组)和 85名正常对照(NC)组的AR、eNOS基因多态性与DN易感性的关系。结果　AR基因的C等位基因、C/C基因型和eNOS基因的T、4a等位基因及T/G、4a/4b基因型频率在DN-组和NC组间差异无统计学意义,而在DN+组则显著高于DN-组(均P<0. 05)。随着携带以上基因型数目的增加,发生DN的相对危险度(OR)也明显增加 (χ2 =8. 43,P<0. 05 )。结论　eNOS基因的T/G、4a/4b基因型和AR基因的C/C基因型可能均为DN的易感基因型;发生DN的相对危险度与携带易感基因型数量有关,三者同时存在时,发生DN的OR值最高。更多还原

【Abstract】 Objective To investigate the relationship between the polymorphisms of both aldose reductase (AR) and endothelial nitric oxide synthase (eNOS) genes in chromosome 7q35 and the susceptibility to diabetic nephropathy (DN) in type 2 diabetes of Han nationality in North China. Methods The C(-106)T in the promoter region of AR gene as well as the G894T in exon 7 and the 27 bp repeat polymorphism in intron 4 of the eNOS gene were investigated in 85 healthy controls and 134 type 2 diabetics with or without DN. The C(-106)T as well as the G894T genotype were determined by PCR RFLP method and sequencing the PCR products. The 27 bp repeat polymorphism alleles were determined by PCR combined with agarose gel electrophoresis and sequencing the PCR products. Results The frequencies of the C allele and C/C genotype in AR gene as well as T allele and T/G genotype in exon 7 and the 4a allele and 4a/4b genotype in intron 4 of eNOS gene were significantly higher in DN+ group than those in DN-group (all P<0.05), however, there was no difference between DN- group and NC group. The odds ratio (OR) of DN was significantly related to the number of susceptible genotype (χ 2=8.43, P<0.05). Conclusion The T/G genotype and 4a/4b genotype in eNOS gene as well as C/C genotype in AR gene are all possibly susceptible genotypes of DN in Chinese type 2 diabetes mellitus. OR of DN is significantly related to the number of susceptible genotype, accordingly coexistence of the three susceptible genotypes shows the highest OR of DN.更多还原