CLU基因多态性与新疆哈萨克族及汉族阿尔茨海默病的相关性研究

摘要

目的 探讨聚集素 (clusterin, CLU) 基因rs11136000位点及rs9331888位点多态性与新疆哈萨克族 (简称哈族) 及汉族散发性阿尔茨海默病 (Alzheimer's disease, SAD) 相关性.方法 运用病例对照研究, 采用Kas P PCR技术和基因测序法测定CLU rs11136000及rs9331888位点的基因型及等位基因.结果 (1) CLU基因rs11136000位点基因型及等位基因分布在SAD及正常对照组差异有统计学意义 (P <0. 05) .哈族SAD组CLU基因rs11136000位点T等位基因及TT基因型频率显著低于对照组 (χ2=8. 809, P=0. 003;χ2=8. 242, P=0. 016) .携带T等位基因者 (TT+TG基因型) 相比携带GG基因型者AD发病风险降低63. 9％ (OR=0. 361, P=0. 007) .汉族SAD CLU基因rs11136000位点基因型及等位基因与对照组之间差异均无统计学意义 (P> 0. 05) . (2) CLU rs9331888位点等位基因 (C、G) 及基因型 (CC、CG、GG) 频率差异无统计学意义 (P> 0. 05) . (3) rs9331888、rs11136000两位点存在连锁不平衡 (D'=0. 764) , 单体型分析显示有C-C、C-G、T-G 3种单体型, 频率分布差异无统计学意义 (P> 0. 05) .结论 CLU基因rs11136000位点多态性与新疆哈族AD发生可能有关, 携带T等位基因对降低AD发病可能有一定的保护作用; CLU基因9331888位点可能与新疆SAD的发生无相关性.%Objective Investigating the assocation between rs11136000 and rs9331888 polymorphisms of clusterin (CLU) gene and sporadic Alzheimer's disease (SAD) in Xinjiang Kazakh and Han nationality. Methods A case-control study, The genotypes and alleles of the CLU rs11136000 and rs9331888 loci were determined by Kas P PCR and gene sequencing. Results (1) The genotype and allele distribution of CLU gene rs11136000 was significantly different between the SAD and the control group (P < 0. 05) . The frequency of T allele and TT genotype in the rs11136000 site of the SAD CLU gene was significantly lower in the Kazakh group than in the control group (χ2= 8. 809, P = 0. 003; χ2= 8. 242, P =0. 016); The TT + TG genotype carrying the T allele was associated with decreased SAD risk, which was 63. 9％ lower than that of the GG genotype (OR = 0. 361, P = 0. 007) . There was no significant difference in the genotypes and alleles of the rs11136000 locus of the CLU gene in the Han nationality SAD (P> 0. 05) . (2) There was no significant difference in the frequencies of CLU rs9331888 alleles (C, G) and genotypes (CC, CG, GG) between the Han and Kazakh nationalities (P>0. 05) . (3) rs9331888 and rs11136000 linkage disequilibrium tests showed that there were linkage disequilibrium between the two sites (D'= 0. 764) . The haplotype analysis showed that there was no statistically significant difference in the frequency distribution of the three haplotypes of C-C、C-G、and T-G. Conclusions (1) The rs111 The rs11136000 polymorphism of CLU gene maybe associated with the development of Xinjiang Kazakh AD. Carrying the T allele (TT + TG genotype) may have a protective effect on the pathogenesis of AD; CLU gene 9331888 may not be significantly related to SAD in Xinjiang.