Association of Polymorphisms in the angiotensin-converting enzyme gene with Alzheimer disease in an Israeli Arab community
Association of Polymorphisms in the angiotensin-converting enzyme gene with Alzheimer disease in an Israeli Arab community
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DOI：
10.1086/503687
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发表时间：
2006-05-01
影响因子：
9.8
通讯作者：
Farrer, LA
中科院分区：
文献类型：
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作者：
Meng, Y;Baldwin, CT;Farrer, LA
一些证据支持血管紧张素转换酶(ACE)在阿尔茨海默病(AD)中的作用。大多数遗传学研究都集中在血管紧张素转换酶基因(DCP1)的Alu插入/缺失(I/D)多态性上，并产生了相互矛盾的结果。我们评估了DCP1中包括I/D变异在内的15个单核苷酸多态(SNPs)与阿尔茨海默病(AD)之间的关系，样本中有92名AD患者和166名来自以色列阿拉伯社区的非痴呆对照。虽然尚无证据表明AD与I/D相关，但我们观察到与rs4343(P=0.00001)和rs4351(P=0.01)SNPs显著相关。单倍型分析显示了与SNP组合rs4343和rs4351相关的显著证据(全局P=7.5×10(-7))。与其他三种单倍型中的任何一种相比，携带这10个SNP的单倍型“GA”(在病例和对照中的频率分别为0.21和0.01)的个体患AD的风险增加45倍(95%可信区间6.0-343.2)。包括I/D在内的更远距离的单倍型更为显著(全局最低P=1.1×10(-12))，但唯一一致关联的等位基因是rs4343和rs4351。这些结果表明，rs4343和rs4351附近的一个变异体调节了该社区对AD的易感性。
Several lines of evidence support for a role of angiotensin converting enzyme (ACE) in Alzheimer disease (AD). Most genetic studies have focused on an Alu insertion/deletion (I/D) polymorphism in the ACE gene (DCP1) and have yielded conflicting results. We evaluated the association between 15 single-nucleotide polymorphisms (SNPs) in DCP1, including the I/D variant, and AD in a sample of 92 patients with AD and 166 nondemented controls from an inbred Israeli Arab community. Although there was no evidence for association between AD and I/D, we observed significant association with SNPs rs4343 (P = .00001) and rs4351 (P = .01). Haplotype analysis revealed remarkably significant evidence of association with the SNP combination rs4343 and rs4351 (global P = 7.5 x 10(-7)). Individuals possessing the haplotype "GA" (frequency 0.21 in cases and 0.01 in controls) derived from these 10 SNPs had a 45-fold increased risk of developing AD (95% CI 6.0-343.2) compared with those possessing any of the other three haplotypes. Longer range haplotypes including I/D were even more significant (lowest global P = 1.1 x 10(-12)), but the only consistently associated alleles were in rs4343 and rs4351. These results suggest that a variant in close proximity to rs4343 and rs4351 modulates susceptibility to AD in this community.