家族性地中海热基因的M694V变体与意大利人群样本中的散发性早发性阿尔茨海默病相关。

The M694V variant of the familial Mediterranean fever gene is associated with sporadic early-onset Alzheimer's disease in an Italian population sample.

作者信息

Arra Mariarosa, Emanuele Enzo, Martinelli Valentina, Minoretti Piercarlo, Bertona Marco, Geroldi Diego

机构信息

Interdepartmental Center for Research in Molecular Medicine, University of Pavia, Pavia, Italy.

出版信息

Dement Geriatr Cogn Disord. 2007;23(1):55-9. doi: 10.1159/000096743. Epub 2006 Nov 6.

DOI:10.1159/000096743

PMID:17090974

Abstract

BACKGROUND

Inflammation is deemed to play a crucial role in the pathogenesis of Alzheimer's disease (AD). We sought to determine whether the proinflammatory M694V mutation of pyrin, the gene responsible for familial Mediterranean fever, could lead to an increased risk for AD.

METHODS

We compared the M694V variant genotypes in 378 sporadic AD patients and 384 healthy control subjects of Italian descent.

RESULTS

After adjustment for potential confounders, the M694V mutation was found to be associated with an increased risk for AD in subjects with an age at onset of 65 years or younger (multivariate-adjusted odds ratio, OR: 3.01, 95% confidence interval, CI: 1.24-6.72, p = 0.021), but not in patients with an age at onset older than 65 years (multivariate-adjusted OR: 0.81, 95% CI: 0.34-1.99, p = 0.847). Kaplan-Meier analysis indicated that AD patients bearing the M694V mutation presented with disease onset 7 years earlier than carriers of the wild-type genotype (log rank = 41.61, p < 0.001).

CONCLUSION

Our data indicate that the M694V sequence variant in the pyrin gene might influence the age at onset of AD in the Italian population.

摘要

背景

炎症被认为在阿尔茨海默病（AD）的发病机制中起关键作用。我们试图确定负责家族性地中海热的基因——吡喃素的促炎M694V突变是否会导致AD风险增加。

方法

我们比较了378例散发性AD患者和384例意大利裔健康对照者的M694V变异基因型。

结果

在对潜在混杂因素进行校正后，发现M694V突变与发病年龄在65岁及以下的受试者患AD的风险增加相关（多变量校正比值比，OR：3.01，95%置信区间，CI：1.24 - 6.72，p = 0.021），但在发病年龄大于65岁的患者中未发现相关（多变量校正OR：0.81，95% CI：0.34 - 1.99，p = 0.847）。Kaplan-Meier分析表明，携带M694V突变的AD患者发病时间比野生型基因型携带者早7年（对数秩检验=41.61，p < 0.001）。