Distribution of functional polymorphic variants of inflammation-related genes RANTES and CCR5 in long-lived individuals

Abstract

Although persistent inflammation has been related to unsuccessful aging, a pro-inflammatory status is the common phenotype in older people. To assess for a genetic component in the inflammatory status of the oldest we studied the distribution of two polymorphic chemokine pathway genes, RANTES and CCR5, in elderly. RANTES −403G/A and RANTES Int1.1T/C polymorphisms and CCR5Δ32 polymorphism were genotyped in 104 elderly and 110 controls. RANTES −403A and RANTES Int1.1C alleles have been associated with pro-inflammatory and anti-inflammatory status, respectively. CCR5Δ32 abrogates functional receptor expression of the pro-inflammatory CCR5-mediated action. Prevalence of RANTES −403G allele, associated in other studies with high RANTES production, was reduced in elderly males, compared with controls. In addition, RANTES pro-inflammatory haplotype −403A-Int1.1T was overrepresented in elderly males, while RANTES anti-inflammatory haplotype −403G-Int1.1C was overrepresented in elderly females. Our results suggest a sex-specific RANTES inflammatory genetic determinant that could contribute to the known sex-related differences in aging.

M.L. was recipient of a fellowship from the University of Lleida. This work was supported by grants to the University of Lleida (J.F., principal investigator) from Fondo de Investigación Sanitaria (FIS, PI051778) and Ministerio de Ciencia e Innovación (CGL 2007-62875).