A genetic-demographic approach reveals male-specific association between survival and tumor necrosis factor (A/G)-308 polymorphism

The (A/G)-308 polymorphism of the tumor necrosis factor α gene (TNF) is associated with age-related diseases, but its influence on longevity is controversial. We genotyped for this polymorphism 747 Italian volunteers (401 women and 346 men, age 19-110 years). By applying a genetic-demographic (GD) approach we found that, in men, the survival function of allele A carriers is lower than that of noncarriers at all the ages (p = .044). After defining (by exploiting again demographic information) three age classes, we found that the frequency of men carrying the A allele decreases with age (p = .019), thus confirming the GD analysis results. The same analyses gave negative results in women. Therefore, allele A has a detrimental effect on life expectancy, and this effect is specific to men. A haplotype analysis carried out in men by screening the TNFa, TNFc, and TNFe microsatellite polymorphisms (spanning about 20 kb) confirmed the association of the TNF region with life expectancy. Copyright 2008 by The Gerontological Society of America.