胰岛素降解酶基因单核苷酸多态性与迟发性阿尔茨海默病关系的研究

Relation between single nucleotide polymorphism of insulin-degrading enzyme gene and late-onset Alzheimer's disease

目的探讨胰岛素降解酶(IDE)基因中与新疆地区迟发性阿尔茨海默病(LOAD)发病相关的可能危险位点。方法选择新疆地区汉族人群168例LOAD患者为LOAD组和170例健康者为对照组,采用直接基因测序的方法比较2组IDE 3个基因位点rs1544210、rs1887922和rs1999764基因型和等位基因频率分布,并对其与LOAD的关系进行相关分析。结果 LOAD组与对照组rs1887922和rs1999764基因型和等位基因频率差异有统计学意义(P<0.05)。LOAD组rs1999764TT基因型和T等位基因明显高于对照组,rs1887922TT基因型和T等位基因明显低于对照组。2组不携带载脂蛋白Eε4等位基因的亚组中,rs1887922和rs1999764各基因型和等位基因频率比较,差异有统计学意义(P<0.01)。rs1544210和rs1999764之间具有显著的连锁不平衡,构成了相对降低LOAD发病风险的单体型rs1544210 G/rs1999764C和未携带载脂蛋白Eε4等位基因时相对危险的单体型rs1544210G/rs1999764T。结论 IDE基因单核苷酸多态性基因位点rs1887922和rs1999764可能与新疆地区汉族人群LOAD发病相关。

Objective To study the relation between single nucleotide polymorphism of insulin-de grading enzyme （IDE） gene and late-onset Alzheimer＇s disease （LOAD） in Xinjiang Uygur Autonomous Region. Methods One hundred and sixty eight LOAD patients served as a I.OAD group and 170 healthy subjects served as a control group in this study. The rs1544210,rs1887922 and rs1999764 genotypes of IDE gene and the distribution of alles were compared by direct gene sequencing. Their relation with LOAD was analyzed. Results The frequencies of rs1887922 and rs1999764 genotypes and alles were significantly higher in LOAD group than in control group （P〈0.05）. The frequencies of rs1999764TT and rs1999764T were significantly higher whereas those of rs18887922T and rs1887922TT were significantly lower in LOAD group than in control group. No apoEε4 alle was found in the two groups. The frequencies of rs1544210 and rs1999764 genotypes and alles were significantly higher in LOAD group than in control group with a significant linkage unbalance,thus forming the rs1544210 G/rs1999764 C haplotypes with a low risk for LOAD and rs1544210G/rs1999764T carrying no apoEε4 allele with a relative risk for LOAD. Conclusion The frequencies of rs1999764 and rs1887922 genotypes of IDE gene are related to LOAD in Xinjiang Han populations.