Interleukin-1beta and interleukin-6 gene polymorphisms as risk factors for AD: a prospective study

Risk of incident dementia from any cause and Alzheimer's disease (AD) in relation to the IL-1beta-511 (C-->T) and IL-6-174 (G-->C) polymorphisms was investigated in an Italian elderly cohort (n=791) with 4 years of follow-up. Analyses were adjusted for socio-demographic confounders (age, gender, education), presence of the Apolipoprotein E-epsilon4 allele, and plasma total homocysteine (tHcy), a newly proposed AD risk factor. No significant association was found for the IL-1beta-511 and IL-6-174 polymorphisms with either dementia or AD. However, in the baseline dementia-free cohort considered as a whole, independently of other confounders, IL-1beta-511 T/T homozygotes had lower plasma tHcy than both heterozygotes (P=0.036) and wild-types (P=0.004). These data do not support the hypothesis that the IL-1-beta-511 and IL-6-174 polymorphisms affect dementia or AD risk. The relationship between the AD risk factor plasma tHcy and the IL-1beta-511 polymorphism was never reported before and might explain previous cross-sectional reports of an association between this polymorphism and AD.