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

Authors: Cardelli M; Cavallone L; Marchegiani F; Oliveri F; Dato S; Montesanto A; Lescai F; Lisa R; De Benedictis G; Franceschi C

Abstract: The (A/G)-308 polymorphism of the tumor necrosis factor alpha 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: Adult; Aged; Aged, 80 and over; Female; Humans; Longevity/*genetics; Male; Middle Aged; *Polymorphism, Genetic; Tumor Necrosis Factor-alpha/*genetics
Journal: The journals of gerontology. Series A, Biological sciences and medical sciences
Volume: 63
Issue: 5
Pages: 454-60
Date: May 31, 2008
PMID: 18511747
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Citation:

Cardelli M, Cavallone L, Marchegiani F, Oliveri F, Dato S, Montesanto A, Lescai F, Lisa R, De Benedictis G, Franceschi C (2008) A genetic-demographic approach reveals male-specific association between survival and tumor necrosis factor (A/G)-308 polymorphism. The journals of gerontology. Series A, Biological sciences and medical sciences 63: 454-60.


Longevity Variant Associations (p-value):
  • rs1800629 (0.019)

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