Abstract
BackgroundInterleukin (IL)-1β 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-1β converting enzyme (ICE), mediates the cleavage of the inactive precursor of IL-1β 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.MethodsWe 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.ResultsThere 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 ε4 allele.ConclusionOur negative findings in the Spanish population argue against the hypothesis that CASP1 genetic variations are causally related to AD risk.
Highlights
Interleukin (IL)-1b is a potent proinflammatory cytokine markedly overexpressed in the brains of patients with Alzheimer’s disease (AD), and involved in development of atherosclerosis and coronary artery disease
The predominant b isoform of IL-1 is generated from an inactive precursor through the action of caspase-1 (CASP1), a cystein protease formerly called IL-1b converting enzyme (ICE), and CASP1 expression appears to be significantly increased in post-mortem brain tissue from patients with AD [3,4,5]
The three CASP1 haplotype tagging SNPs (htSNPs) were in complete linkage disequilibrium (LD) with each other forming one block, and they exhibited a pattern of reduced haplotype diversity, with only four haplotypes captured that did not differ between AD and control groups (Table 2)
Summary
Interleukin (IL)-1b is a potent proinflammatory cytokine markedly overexpressed in the brains of patients with Alzheimer’s disease (AD), and involved in development of atherosclerosis and coronary artery disease. Caspase-1 (CASP1), formerly called IL-1b converting enzyme (ICE), mediates the cleavage of the inactive precursor of IL-1b into the biologically active form. A chronic inflammatory process might contribute to the neurodegeneration associated with Alzheimer’s disease (AD), by overexpression of cytokines, such as interleukin-1 (IL-1), and other inflammatory molecules in activated microglia surrounding amyloid plaques [1]. The predominant b isoform of IL-1 is generated from an inactive precursor through the action of caspase-1 (CASP1), a cystein protease formerly called IL-1b converting enzyme (ICE), and CASP1 expression appears to be significantly increased in post-mortem brain tissue from patients with AD [3,4,5]. CASP1 messenger RNA expression has been closely associated with neurofibrillary tangle and, to a lesser extent, amyloid plaque
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