乙醛脱氢酶ALDH7A1基因多态性与2型糖尿病的相关性研究

Research on the correlation of the acetaldehyde dehydrogenase ALDH7A1 gene poly morphism and type 2 diabetes mellitus

目的探讨ALDH7A1基因多态性位点rs2306619、rs2306618、rs12514417、rs2306617、rs4379190与中国湖北随州汉族居民2型糖尿病(T2DM)的相关性。方法收集220名健康对照者和240例T2DM患者,所有研究对象均来自湖北随州汉族城镇居民。从外周血的白细胞中应用标准法提取DNA。通过设计测序引物对相邻的5个所选位点(rs2306619、rs2306618、rs12514417、rs2306617、rs4379190)进行基因扩增,然后直接送样测序,采用SHEsis软件进行统计分析ALDH7A1基因5个位点的单核甘酸多态性及连锁不平衡,分析糖尿病组与对照组5个位点等位基因频率和基因型频率的差异及构建单体型。结果 5个位点的最低等位基因频率分别是0.492、0.084、0.124、0.277、0.259,连锁不平衡检验发现5个位点呈现强的连锁不平衡,ALDH7A1基因的5个位点基因的等位基因频率和基因型频率在2组中差异均无统计学意义,单体型分析发现C-A-A-A-T、T-A-A-A-T、T-A-AG-C、T-A-C-A-T、T-G-A-G-C 5种单体型,并且这5种单体型在糖尿病组和对照组差异无统计学意义。结论 ALDH7A1基因的5个多态性位点可能不是湖北随州汉族2型糖尿病患者的易感基因;本研究结果尚需在更大规模人群中进一步验证。

Objective To study the correlation of ALDHTA1 gene polymorphism locus rs2306619, rs2306618, rs12514417, rs2306617 and rs4379190 with type 2 diabetes mellitus among Chinese Hubei Snizhou Han population. Methods A total of 220 healthy controls and 240 unrelated patients with type 2 diabetes mellitus were enrolled, and all of them were from Han urban residents in Hubei Suizhou. The DNA was extracted from white blood cell of peripheral blood by standard method. The 5 polymorphism loci （rs2306619, rs2306618, rs12514417, rs2306617 and rs4379190） were amplified through designed sequence primer, and the sequence analysis was performed. The single nncleotide polymorphism and linkage disequilibrium of ALDH＇IA1 gene 5 polymorphism loci were analyzed statistically by SHEsis software. The differences and haplotypes of 5 locus allele frequencies and genotype frequencies were compared between type 2 diabetes mellitus group and control group. Results Five locus minimum allele frequencies were 0.492, 0.084, 0. 124, 0.277 and 0. 259. Linkage disequilibrium test showed 5 loci with strong linkage disequilibrium. The ALDHTA1 geneS5 locus allele frequencies and genotype frequencies in the 2 groups had no statistical significance. Haplotype analysis showed C-A-A-A-T, T- A- A- A-T, T-A-A-G-C, T-A-C-A-T and T-G-A-G-C haplotypes, and the 5 haplotypes in type 2 diabetes mellitus group and control group had no statistical significance. Conclusions The 5 polymorphism loci of ALDITIA1 gene may be the susceptibility genes for the patients with type 2 diabetes mellitus in Chinese Hubei Suizhou Han population. The results of the present study are needed to validate in larger populations.