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


CONCLUSIONS
Our negative findings in the Spanish population argue against the hypothesis that CASP1 genetic variations are causally related to AD risk.
Vázquez-Higuera
José Luis
JL
Neurology Service and CIBERNED, Marqués de Valdecilla University Hospital, Santander, Spain.
Rodríguez-Rodríguez
Eloy
E
Sánchez-Juan
Pascual
P
Mateo
Ignacio
I
Pozueta
Ana
A
Martínez-García
Ana
A
Frank
Ana
A
Valdivieso
Fernando
F
Berciano
José
J
Bullido
María J
MJ
Combarros
Onofre
O
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D020170:Caspase 1 / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012737:Sex Factors
D053327:Apolipoprotein E4; D053583:Interleukin-1beta; D020170:Caspase 1