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A Genetic–Demographic Approach Reveals Male-Specific Association Between Survival and Tumor Necrosis Factor (A/G)-308 Polymorphism

¹ Italian National Research Center on Aging, Ancona, Italy.
² Department of Human Genetics, McGill University, Montreal, Canada.
³ Department of Cell Biology, University of Calabria, Italy.
⁴ Department of Experimental Pathology and ⁵ Centro Interdipartimentale "L. Galvani," University of Bologna, Italy.
⁶ ER-GenTech laboratory, Ferrara, Italy.

Address correspondence to Maurizio Cardelli, PhD, Department of Gerontological Research, Italian National Research Center on Aging (I.N.R.C.A), Via Birarelli 8, 60100 Ancona, Italy. E-mail: maucard{at}libero.it

The (A/G)-308 polymorphism of the tumor necrosis factor 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.

Key Words: TNF(A/G)-308 polymorphism • TNF microsatellites • Longevity • Genetic-demographic approach