A Genetic-Demographic Approach Reveals Male-Specific Association Between Survival and Tumor Necrosis Factor (A/G)-308 Polymorphism
Open Access
- 1 May 2008
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences
- Vol. 63 (5), 454-460
- https://doi.org/10.1093/gerona/63.5.454
Abstract
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.Keywords
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