Caspase-1 基因变异与阿尔茨海默病风险无关。
Caspase-1 genetic variation is not associated with Alzheimer's disease risk.
机构信息
Neurology Service and CIBERNED, Marqués de Valdecilla University Hospital, Santander, Spain.
出版信息
BMC Med Genet. 2010 Feb 25;11:32. doi: 10.1186/1471-2350-11-32.
BACKGROUND
Interleukin (IL)-1beta is a potent proinflammatory cytokine markedly overexpressed in the brains of patients with Alzheimer's disease (AD), and also involved in development of atherosclerosis and coronary artery disease. Caspase-1 (CASP1), formerly called IL-1beta converting enzyme (ICE), mediates the cleavage of the inactive precursor of IL-1beta into the biologically active form. CASP1 genetic variation (G+7/in6A, rs501192) has been associated with susceptibility to myocardial infarction and cardiovascular death risk. We examined the contribution of this gene to the susceptibility for AD.
METHODS
We examined genetic variations of CASP1 by genotyping haplotype tagging SNPs (htSNPs) (rs501192, rs556205 and rs530537) in a group of 628 Spanish AD cases and 722 controls.
RESULTS
There were no differences in the genotypic, allelic or haplotypic distributions between cases and controls in the overall analysis or after stratification by age, gender or APOE epsilon4 allele.
CONCLUSION
Our negative findings in the Spanish population argue against the hypothesis that CASP1 genetic variations are causally related to AD risk.
背景
白细胞介素 (IL)-1β 是一种强效的促炎细胞因子，在阿尔茨海默病 (AD) 患者的大脑中过度表达，也与动脉粥样硬化和冠心病的发展有关。半胱氨酸蛋白酶-1 (CASP1)，以前称为白细胞介素-1β 转换酶 (ICE)，介导将 IL-1β 的无活性前体切割成具有生物活性的形式。CASP1 基因变异 (G+7/in6A，rs501192) 与心肌梗死易感性和心血管死亡风险增加有关。我们研究了这种基因对 AD 易感性的贡献。
方法
我们通过基因分型单倍型标记 SNP（htSNP）（rs501192、rs556205 和 rs530537），在一组 628 名西班牙 AD 病例和 722 名对照中检查了 CASP1 的遗传变异。
结果
在总体分析或按年龄、性别或 APOE ε4 等位基因分层后，病例和对照组之间在基因型、等位基因或单倍型分布方面均无差异。
结论
我们在西班牙人群中的阴性发现表明，CASP1 基因变异与 AD 风险没有因果关系。
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