title: Evidence for depletion of CASP5 Ala90Thr heterozygous genotype in aged subjects.
abstract: 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.
authors.affiliation: N.N. Petrov Institute of Oncology, Pesochny-2, St.-Petersburg, Russia.
authors.forename: Yulia M
authors.initials: YM
authors.lastname: Ulybina
authors.forename: Ekatherina Sh
authors.initials: ESh
authors.lastname: Kuligina
authors.forename: Nathalia V
authors.initials: NV
authors.lastname: Mitiushkina
authors.forename: Nathalia Yu
authors.initials: NY
authors.lastname: Sherina
authors.forename: Grigoriy A
authors.initials: GA
authors.lastname: Yanus
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Gorodnova
authors.forename: Anna S
authors.initials: AS
authors.lastname: Katanugina
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Koloskov
authors.forename: Alexandr V
authors.initials: AV
authors.lastname: Togo
authors.forename: Evgeny N
authors.initials: EN
authors.lastname: Imyanitov
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D017209:Apoptosis; D020169:Caspases / Q000235:genetics*; D017931:DNA Primers; D005787:Gene Frequency; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012907:Smoking / Q000453:epidemiology
chemical_list: D017931:DNA Primers; C099217:CASP5 protein, human; D020169:Caspases