醛糖还原酶基因5′端(AC)n多态性与糖尿病肾病、糖尿病周围神经病变的相关性

Relationship between the Polymorphism of (AC)n in 5′ End of the Aldose Reductase Gene and the Susceptibility of Diabetic Nephropathy, Diabetic Peripheral Neuropathy

目的:探讨2型糖尿病(DM)醛糖还原酶(AR)基因5′端的(AC)n的多态性与糖尿病肾病(DN)、糖尿病周围神经病变(DPN)易感性的关系。方法:选择本院2型DM患者119例为DM组,根据其同时伴(+)或不伴(-)DN与DPN,将DM组分为四个亚组:DN-/DPN-组、DN-/DPN+组、DN+/DPN-组、DN+/DPN+组;同时选取健康体检者62例为正常对照(CON)组。采用聚合酶链反应(PCR)及尿素/甲酰胺聚丙烯酰胺凝胶电泳银染显色法分析各组AR基因的二核苷酸(AC)n串联重复序列的多态标记,比较各组间等位基因频率和基因型频率。结果:各组中Z-2等位基因频率比较差异有统计学意义(P<0.05),其中在DN+/DPN+组最高,在DN-/DPN-组最低;Z+2等位基因频率在DN-/DPN-组显著增高,在DN+/DPN+组显著降低,两组比较差异有统计学意义(P<0.01);纯合子Z-2/Z-2基因型频率在DN+/DPN+组显著高于其余各组,而纯合子Z+2/Z+2基因型频率在DN-/DPN-组显著高于其余各组。结论:Z+2等位基因是2型糖尿病患者发生DN及DPN的保护性基因;Z-2等位基因是DN易感基因,而病程和Z-2等位基因可能共同促进了DPN的发生。

Objective：To study the relationship between the polymorphism of（AC）n in 5′end of the AR gene and the susceptibility of diabetic nephropathy,diabetic peripheral neuropathy in type 2 DM. Method：Chosen our hospital 119 patients with type 2 DM for DM group,at the same time, according to its companion（＋）or without（-）DN and DPN,DM group were divided into four subgroups：DN/DPN-group,the DN/DPN＋group,DN＋/DPN-group,the DN＋/DPN＋group;At the same time chosen 62 cases of healthy check-up as normal control group（CON）. The polymerase chain reaction（PCR）by urea,formamide and polyacrylamide gel electrophoresis,silver dye chromogenic method AR gene dinucleotide（AC）n polymorphism of tandem repeat sequence tags were used and analyze in each group,compared the allele frequency and genotype frequency of each group. Result：The frequence of Z-2 allele in DN＋/DPN＋group was much higher than that in the other groups（P〈0.05）. The frequence of Z＋2 allele in group DN＋/DPN＋was much lower than that in the other groups（P〈0.01）;Z-2/Z-2 genotype frequency in the DN＋/DPN＋group was significantly higher than that of the other groups,and Z＋2/Z＋2 genotype frequency in the DN-/DPN-group was significantly higher than the other groups. Conclusion：AR gene alleles are associated with the development of diabetic microangiopathy. The Z＋2 allele protect against the development and progression of DN and DPN. Whereas, the Z-2 allele may be a risk factor for the developing of DN. Both the course of DM and Z-2 allele promote the development of DNP.