Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations
Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations
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DOI：
10.1016/j.neurobiolaging.2010.11.022
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发表时间：
2011-04-01
影响因子：
4.2
通讯作者：
Amouyel, Philippe
中科院分区：
文献类型：
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作者：
Lambert, Jean-Charles;Zelenika, Diana;Amouyel, Philippe
最近的全基因组关联研究已经确定了5个基因座(BIM、CLU、CR1、EXOC3L2和PICALM)是阿尔茨海默病(AD)的遗传决定因素。我们试图在3个不同的欧洲人群(来自芬兰、意大利和西班牙)中确认这些基因与AD风险之间的关联。因为已经在这些人群中分析了CLU和CRI，所以我们的研究仅限于BIN1、EXO2CL3和PICALM。在2816例AD患者和2706例对照中，我们明确复制了rs744373(BIN1)和rs541458(PICALM)基因多态性与AD风险的关联(优势比[OR]=1.26，95%可信区间[CI][1.15-1.38]，p=2.9×10(-7)，OR=0.80，95%CI[0.74-0.88]，p=4.6×10(-7))。在Meta分析中，rs597668(EXOC3L2)也与AD风险相关，但程度较小(OR=1.19，95%CI[1.06-1.32]，p=2.0×10(-3))。然而，这一信号似乎并不独立于APOE。总而言之，我们确认了BIN！和PICALM是AD的遗传决定因素，而EXOC3L2的潜在参与有待进一步研究。(C)2011 Elsevier Inc.保留所有权利。
Recent genome-wide association studies have identified 5 loci (BIM, CLU, CR1, EXOC3L2, and PICALM) as genetic determinants of Alzheimer's disease (AD). We attempted to confirm the association between these genes and the AD risk in 3 contrasting European populations (from Finland, Italy, and Spain). Because CLU and CRI had already been analyzed in these populations, we restricted our investigation to BIN1, EXO2CL3, and PICALM. In a total of 2816 AD cases and 2706 controls, we unambiguously replicated the association of rs744373 (for BIN1) and rs541458 (for PICALM) polymorphisms with the AD risk (odds ratio [OR] = 1.26, 95% confidence interval [Cl] [1.15-1.38], p = 2.9 X 10(-7), and OR = 0.80, 95% CI [0.74-0.88], p = 4.6 X 10(-7), respectively). In a meta-analysis, rs597668 (EXOC3L2) was also associated with the AD risk, albeit to a lesser extent (OR = 1.19, 95% Cl [1.06-1.32], p = 2.0 X 10(-3)). However, this signal did not appear to be independent of APOE. In conclusion, we confirmed that BIN! and PICALM are genetic determinants of AD, whereas the potential involvement of EXOC3L2 requires further investigation. (C) 2011 Elsevier Inc. All rights reserved.