在对比的欧洲人群中，BIN1 和 PICALM 与 AD 风险的关联证据。

Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations.

机构信息

INSERM U744, Lille, France.

出版信息

Neurobiol Aging. 2011 Apr;32(4):756.e11-5. doi: 10.1016/j.neurobiolaging.2010.11.022. Epub 2011 Jan 8.

DOI:10.1016/j.neurobiolaging.2010.11.022

PMID:21220176

Abstract

Recent genome-wide association studies have identified 5 loci (BIN1, 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 CR1 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 [CI] [1.15-1.38], p = 2.9 × 10(-7), and OR = 0.80, 95% CI [0.74-0.88], p = 4.6 × 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% CI [1.06-1.32], p = 2.0 × 10(-3)). However, this signal did not appear to be independent of APOE. In conclusion, we confirmed that BIN1 and PICALM are genetic determinants of AD, whereas the potential involvement of EXOC3L2 requires further investigation.

摘要

最近的全基因组关联研究已经确定了 5 个基因座（BIN1、CLU、CR1、EXOC3L2 和 PICALM）作为阿尔茨海默病（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。由于 CLU 和 CR1 已经在这些人群中进行了分析，我们将研究范围限制在 BIN1、EXO2CL3 和 PICALM 上。在总共 2816 例 AD 病例和 2706 例对照中，我们明确地复制了 rs744373（BIN1）和 rs541458（PICALM）多态性与 AD 风险之间的关联（比值比[OR] = 1.26，95%置信区间[CI] [1.15-1.38]，p = 2.9×10(-7)，和 OR = 0.80，95%CI [0.74-0.88]，p = 4.6×10(-7)）。在荟萃分析中，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，这个信号似乎并不独立于 APOE。总之，我们证实 BIN1 和 PICALM 是 AD 的遗传决定因素，而 EXOC3L2 的潜在作用需要进一步研究。