Evidence for depletion of CASP5 Ala90Thr heterozygous genotype in aged subjects

Exp Gerontol. 2010 Sep;45(9):726-9. doi: 10.1016/j.exger.2010.04.007. Epub 2010 Apr 29.


Our previous studies, which included genotyping of multiple coding apoptotic gene polymorphisms, unexpectedly demonstrated a depletion of heterozygous CASP5 Ala90Thr (rs507879, c.268 G>A) genotypes in elderly subjects. Present investigation was aimed to validate this trend. An analysis of 510 subjects aged 75-103years revealed 205 (40%) CASP5 Ala90Thr heterozygotes as compared to 254 (50%) expected from the minor allele frequency 0.470 (p=0.000014). This deviation was not observed in 549 middle-aged (18-50years) controls (270 (49%) heterozygotes observed vs. 274 (50%) expected; minor allele frequency 0.475; p=0.743). Unfavorable significance of CASP5 heterozygous genotype may be explained by the role of the caspase-5 in inflammation-related processes. Almost all prior gene-longevity association studies focused on discrimination between "good" and "bad" gene variants. Here we present a distinct situation, where the combination of alternative alleles (i.e., heterozygosity) appears to be unfavorable as compared to the homozygous carriership of either gene variant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Substitution
  • Apoptosis
  • Caspases / genetics*
  • DNA Primers
  • Gene Frequency
  • Genotype
  • Heterozygote
  • Homozygote
  • Humans
  • Longevity / genetics*
  • Lung Neoplasms / genetics
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Smoking / epidemiology


  • DNA Primers
  • CASP5 protein, human
  • Caspases