Caspase-1 genetic variation is not associated with Alzheimer's disease risk

Background: Interleukin (IL)-1 beta 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-1 beta converting enzyme (ICE), mediates the cleavage of the inactive precursor of IL-1 beta 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 epsilon 4 allele. Conclusion: Our negative findings in the Spanish population argue against the hypothesis that CASP1 genetic variations are causally related to AD risk.