醛糖还原酶基因启动子区C-106T多态性与2型糖尿病患者视网膜病变易感性的研究

The study on the relationship between the c-106t polymorphism in aldose reductase gene promoter region and the susceptibility of retinopathy in type 2 diabetes mellitus

目的 研究中国北方汉族人 2型糖尿病视网膜病变 (DR)的易感性与醛糖还原酶 (AR)基因启动子区C 10 6T多态性的相关性 ,并探讨此多态性与AR基因 5′端 (AC)n多态性的连锁关系。 方法 2型糖尿病 (T2DM)患者 116例 ,分为无微血管并发症 (NDC)组和糖尿病视网膜病变 (DR)组 ,提取外周血基因组DNA ,经PCR后用限制性内切酶BfαⅠ 5U进行酶切 ,酶切产物于 3 %琼脂糖凝胶电泳 ,用紫外凝胶成像系统GDS 76 0 0S观察结果。 结果 NDC组和DR组患者均发现 2种等位基因C T ,三种基因型CC、CT和TT ,CC基因型频率在DR组明显高于NDC组 ( 6 4.0 %vs 43.9%,P <0 .0 5 ) ,CT基因型频率在DR组明显低于NDC组 ( 30 %vs 5 4%,P <0 .0 1) ;Z - 2 C单倍型频率在DR组明显高于NDC组 ( 37.0 %vs 3 .0 %,P <0 .0 1) ,Z +2 C和Z +2 T单倍型频率在DR组明显低于NDP组 ( 11.0 %vs 42 .0 %,P <0 .0 1;2 .0 %vs 14.0 %,P <0 .0 5 )。 结论 CC基因型可能增加DR易感性 ,CT基因型可能减低DR易感性 ,且该多态性位点可能与AR基因 5′端 (AC)n多态性之间存在连锁不平衡。

Objective To study the relationship between the C-106T polymorphism in aldose reductase (AR)gene and the susceptibility of retinopathy in type 2 DM and the linkage of the C-106T polymorphism with (AC)n repeat polymorphic marker at the 5'end of AR gene. Methods 116 patients with type 2 DM were divided into no diabetic complication (NDC) group and diabetic retinopathy(DR)group. PCR were performed using genomic DNA as template. PCR products were digested with restriction enzyme Bfα. Genotypes were determined by electrophresis on 3% agarose gel using gel documentation and analysis system. Results Two alleles C/T and three genotypes CC,CT and TT were found. The frequency of CC genotype was significantly higher in DR group than that in NDC group (64.0% vs 43.9%, P<0.05) and the frequency of CT genotype was significantly lower in DR group than that in NDC group (30.0% vs 54.0%, P<0.01). The frequency of Z-2/C haplotypes was significantly higher in DR group than that in NDC group (37.0% vs 3.0%, P<0.001) and the frequency of Z+2/C and Z+2/T haplotype was significantly lower in DR group than that in NDC group (11.0% vs 42.0%, P<0.01 and 2.0% vs 14.0%, P<0.05 respectively). Conclution CC genotype might increase the susceptibility of DR whereas CT genotype might decrease the susceptibility of DR. The C-106T polymorphism and the (AC)n polymorphism might be in linkage disequilibrium.