Human Molecular Genetics, Vol 7, 187-194, Copyright © 1998 by Oxford University Press
R Ivanova, N Henon, V Lepage, D Charron, E Vicaut and F Schachter
In an effort to reassess the contribution of HLA-DRB1 polymorphisms to
inter-individual variations of human longevity, we have compared their
genotypic distributions between longevous and adult control groups in the
French population. The longevous groups included two independent cohorts
totalling 533 centenarians, and 163 nonagenarian siblings. Allelic
distributions were significantly different between controls and longevous
groups. Three individual alleles were mostly responsible for these
differences: DR7, DR11 and DR13. Multivariate logistic analyses were
performed in order to sort out interactions between gender- and
age-specific genetic effects. DR7 frequency was elevated in longevous men,
in centenarians as well as nonagenarian siblings [OR = 1.72 (1.2- 2.5)].
DR11's influence on longevity displayed a significant interaction with sex,
with an increase in women from longevous sibships [OR = 2.03 (1.4-3.0)].
DR13's frequency was increased in centenarians of both genders [OR = 1.46
(1.2-1.75)]. These results are discussed in the context of other
pathophysiological effects of the implicated alleles. Our data support the
direct involvement of three HLA-DR alleles in survival at very old ages.
Two allele-specific effects on longevity appear to depend on gender and one
on familial status for aggregation of this trait. The latter is an original
finding for humans.
ARTICLES
HLA-DR alleles display sex-dependent effects on survival and discriminate between individual and familial longevity
Laboratoire d'Histocompatibilite, Hopital Saint-Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France.
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