中国汉族人群细胞间黏附分子1基因rs5498(A/G K469E)和rs1799969(G/A R241G)多态性与糖尿病周围神经病变的关系

摘要

目的 探讨细胞间黏附分子1(ICAM-1)基因单核苷酸多态性(SNP)与糖尿病周围神经病变(DPN)的相关性.方法 选取2013年6月—2014年12月我院收治的607例2型糖尿病患者,其中DPN组295例,非DPN组312例.采用TaqMan等位基因分型法测定患者rs5498(A/G K469E)和rs1799969(G/A R241G)基因型,分析组间2个SNPs位点的基因型分布以及不同遗传模型对DPN患者发病的影响.结果 2组rs5498(A/G K469E)和rs1799969(G/A R241G)基因型频率分布均符合Hardy-Weinberg平衡.非DPN组与DPN组rs1799969(G/A R241G)主要以GG型为主,分别为96.8%和99.0%;rs5498 A/G K469E以AA型和AG型为主(非DPN组:AA 48.7%,AG 39.4%;DPN组:AA 51.5%,AG 41.7%).2组rs5498(A/G K469E)和rs1799969(G/A R241G)基因型分布和等位基因频率比较差异无统计学意义(P>0.05).遗传模型分析显示rs5498(A/G K469E)显性模型(AA+AG)/GG和加性模型GG/AA中,携带A等位基因与DPN的易感性有关(校正OR分别为1.585和1.575,均P<0.05),rs1799969(G/A R241G)与DPN发病无明显关系.结论 ICAM-1基因SNP rs5498(A/G K469E)与2型糖尿病的DPN并发症相关,携带A等位基因可能是一个危险因素.%Objective To investigate the association of genetic polymorphisms of intercellular adhesion molecule 1 (ICAM-1) with diabetic peripheral neuropathy (DPN). Methods A total of 607 type 2 diabetes patients from the Affiliated Hospital of Weifang Medical University were enrolled in this study between June 2013 and December 2014. Rs5498 (A/G K469E) and rs1799969 (G/A R241G) in the ICAM-1 gene were genotyped by using TaqMan allelic discrimination in 295 patients with DPN and 312 subjects without DPN. The distribution of these two SNPs and the genetic influence of ICAM-1 gene polymorphisms on the development of DPN were conducted. Results Genotype distributions of both SNPs were coincided with Hardy-Weinberg equilibrium in the two groups. SNP rs1799969 (G/A R241G) in the ICAM-1 gene showed a high GG genotypic frequency at 96.8%(non DPN) and 99.0%(DPN) respectively. SNP rs5498 (A/G K469E) represented AA and AG genotypes. The values were AA 48.7%/AG 39.4%in non DPN group and AA 51.5%/AG 41.7%in DPN group. There were no significant differences in genotypic distributions and allele frequencies of SNPs rs1799969 (G/A R241G) and rs5498 (A/G K469E) between the patients with DPN group and patients without DPN group (P>0.05). The dominant(AA+AG)/GG and additive (GG/AA) models of rs5498 (A/G K469E) were associated with higher risk of DPN (ORadjusted=1.585, 1.575 respectively, P<0.05). To carry A allele was related to the susceptibility of DPN. There was no such association in genetic models of rs1799969 (G/A R241G) and DPN pathogenesis. Conclusion The present study provides evidence that SNP rs5498 E469K (A/G) in the ICAM-1 gene is associated with susceptibility of DPN, and the carrying A allele appears to be a risk of DPN.