CALHM1 P86L Polymorphismis Associated with Late-Onset Alzheimer's Disease in a Recessive Model
CALHM1 P86L Polymorphismis Associated with Late-Onset Alzheimer's Disease in a Recessive Model
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DOI：
10.3233/jad-2010-1357
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发表时间：
2010-01-01
影响因子：
4
通讯作者：
Ruiz, Agustin
中科院分区：
文献类型：
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作者：
Boada, Merce;Antunez, Carmen;Ruiz, Agustin
最近的一项研究报告称，编码非同义 SNP P86L (rs2986017) 的 CALHM1 基因会增加患阿尔茨海默病 (AD) 的风险。我们调查了来自西班牙的 2470 名个体的这种遗传变异，以对拟议的 SNP 标记进行独立的复制研究。通过应用隐性模型，我们在病例对照研究中观察到 P86L 突变与迟发性 AD (LOAD) 易感性之间存在关联的微弱证据 (OR - 1.38 C.I. = [1.01-1.89])。现有研究的荟萃分析也支持 CALHM1 P86L 变异的隐性模型，并提供研究之间异质性的证据。重要的是，我们发现 P86L 纯合 LOAD 患者的 AD 发病调整平均年龄明显早于其他患者（P86L 纯合携带者为 77.01 +/- 6.1，其余患者为 79.0 +/- 6.0，p = 0.002）。我们得出的结论是，CALMH1 基因可能会增加我们研究人群的 AD 风险。观察到的遗传模型（隐性）和估计的影响程度都意味着迄今为止进行的几乎所有研究都明显不足以检测这种影响，并强调了对有希望的遗传信号进行随访、复制和荟萃分析的重要性。
CALHM1 gene coding non-synonymous SNP P86L (rs2986017) was reported to increase the risk of Alzheimer's disease (AD) in a recent study. We have investigated this genetic variant in 2470 individuals from Spain to conduct an independent replication study of the proposed SNP marker. By applying a recessive model, we observed weak evidence of an association between P86L mutation and late-onset AD (LOAD) susceptibility in our case-control study (OR - 1.38 C.I. = [1.01-1.89]). Meta-analysis of available studies also supports a recessive model for CALHM1 P86L variant and provides evidence of between study heterogeneity. Importantly, we found that adjusted mean age at AD onset in P86L homozygous LOAD patients was significantly earlier that in the rest of patients (77.01 +/- 6.1 for P86L homozygous carriers versus 79.0 +/- 6.0 for the rest of patients, p = 0.002). We concluded that the CALMH1 gene may contribute to AD risk in our study population. The observed genetic model (recessive) and the estimated magnitude of the effect both imply that virtually all studies performed to date were markedly underpowered to detect this effect and underscore the importance of follow up, replication, and meta-analyses of promising genetic signals.