Opposite effects of interleukin 10 common gene polymorphisms in cardiovascular diseases and successful ageing: genetic background of male centenarians protective against coronary heart disease

Abstract

Many aspects of ageing involve inflammatory processes. We evaluated the association with longevity of alleles of IL10 and TNFa, known to have opposite functions in inflammatory reactions, IL-10 acting predominantly as an anti-inflammatory and TNF-a as a proinflammatory factor. The number of male centenarians homozygous for the –1082G genotype, suggested to be associated with high IL-10 production, was significantly increased in comparison with younger control subjects. No significant differences were observed between women and controls. The genotypic frequencies of the TNFa promoter SNPs 308G and 308A, suggested to be associated with low and high TNF-a production respectively, were not significantly different between centenarians and controls. The evaluation of combined IL10 and TNFá genotypes showed that there was a significant increase of the “anti-inflammatory” (IL10 -1082GG/TNF a -308GG) genotype in centenarian men over controls. Inflammatory markers predict disability and mortality in elderly cohorts and a persistent inflammatory state has been proposed to be involved in the causal pathway of certain age related chronic conditions. Thus, it is intriguing that the possession of an “anti-inflammatory” genotype is significantly increased in male centenarians