α2-巨球蛋白基因Ⅰ1000Ⅴ、苷酸缺失多态与阿尔茨海默病的相关性研究

Relationship between alpha-2 macroglobulin gene polymorphism and Alzheimer′s disease

目的 探讨上海地区汉族人群中α2 巨球蛋白基因 (A2M)Ⅰ 10 0 0Ⅴ、苷酸缺失多态(Ins/Del多态 )与阿尔茨海默病 (AD)发病风险的关系。方法 采用聚合酶链反应和限制性片段长度多态方法 ,于 116例AD患者 (AD组 )和 135名正常人 (对照组 )中检测A2M基因两种多态各基因型及等位基因的频率。通过比值比 (OR)的计算作疾病关联分析。结果 AD组与对照组在A2M基因Ⅰ10 0 0Ⅴ多态Ⅰ /Ⅴ基因型分布的差异有显著性 (χ2 =3 90 5 ,df=1,P =0 0 4 8) ,但无Ins/Del多态分布的差异。A2M基因Ⅰ /Ⅴ基因型与AD呈接近显著性的关联 [(OR =2 2 5 ,95 %可信区间 (95 %CI)∶0 99～ 5 0 9,χ2 =3 76 ,P =0 5 2 ) ];按apoEε4基因分层后 ,仅非ε4型人群中存在Ⅰ /Ⅴ基因型、Ⅴ等位基因与AD的关联 (Ⅰ /Ⅴ基因型 :OR =2 98,95 %CI∶1 16～ 7 6 4 ,χ2 =6 16 ,P =0 0 13;Ⅴ等位基因 :OR =2 77,95 %CI :1 12～ 6 87,χ2 =4 82 ,P =0 0 39)。A2M基因Ins/Del多态与AD间无相关 (P >0 0 5 ) ;即使按apoEε4基因分层后 ,AD组和与照组间也无差异。结论 上海地区汉族人群中A2M基因Ⅰ 10 0 0Ⅴ多态可能构成AD的一种疾病易感因子 。

Objective The present study was to investigate the relationship between Alzheimer′s disease and two variants in alpha 2 macroglobulin gene (A2M), Ⅰ 1000 Ⅴ and Ins/Del polymorphisms, in a Chinese Han population in Shanghai area Methods The two A2M gene polymorphisms in 116 AD cases and 135 healthy subjects were detected with polymerase chain reaction and restriction fragment length polymorphism The polymorphic distribution in AD cases and normal controls was compared with χ 2 test, and the odds ratio was calculated for association analysis Results Genotypic distribution of the A2M Ⅰ 1 000 Ⅴ, but not Ins/Del polymorphism, was significant different between AD cases and controls (χ 2=3 905, df =1, P =0 048) The Ⅰ/Ⅴ genotype was associated with AD ( OR =2 25, 95% CI : 0 99-5 09, P =0 52) After stratification according to the apoE ε 4 status, the association only appeared in the non ε 4 group (for Ⅰ/Ⅴ genotype: OR =2 98, 95% CI : 1 16-7 64, χ 2=6 16, P =0 013; for V allele: OR =2 77, 95% CI : 1 12-6 87, χ 2=4 82, P =0 039) Conclusion It is suggested that A2M gene Ⅰ 1 000 Ⅴ polymorphism may be a susceptibility factor for AD, which independent of apoE ε 4