Memory Clinic of Fundació ACE, Institut Català de Neurociencies Aplicades, Barcelona, Spain.
J Alzheimers Dis. 2010;20(1):247-51. doi: 10.3233/JAD-2010-1357.
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.
CALHM1 基因编码的非同义 SNP P86L(rs2986017)在最近的一项研究中被报道会增加阿尔茨海默病(AD)的风险。我们已经在来自西班牙的 2470 个人中研究了这个遗传变异，以对提议的 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 突变与晚发性 AD(LOAD)易感性之间存在微弱的关联证据(OR=1.38，CI=[1.01-1.89])。对现有研究的荟萃分析也支持 CALHM1 P86L 变体的隐性模型，并提供了研究间异质性的证据。重要的是，我们发现 P86L 纯合子 LOAD 患者的 AD 发病年龄调整均值明显早于其他患者(77.01 +/- 6.1 岁为 P86L 纯合子携带者，79.0 +/- 6.0 岁为其他患者，p=0.002)。我们得出结论，在我们的研究人群中，CALMH1 基因可能会导致 AD 风险增加。观察到的遗传模型(隐性)和估计的效应大小都表明，迄今为止进行的几乎所有研究都明显没有足够的效力来检测到这种效应，这突显了对有前途的遗传信号进行随访、复制和荟萃分析的重要性。
