Familial versus sporadic longevity and MHC markers

We have studied the polymorphism of HLA-A, B, in 2 elderly populations (gre ater than or equal to 90 years) compared to a control series of 429 healthy unrelated individuals less advanced in age. The aged population issued fro m the CHRONOS cohort consisted of 336 centenarians without familial history of longevity, and 102 nonagenarians index cases randomly selected from fam ilies. Almost all individuals (310) were previously typed for HLA-DRB1. The increased allelic frequency of HLA DR11 was observed in familial nonage narians (18.3%) compared to controls (10%) (p < .001) and to sporadic cente narians (11.8%). Concerning HLA Class I alleles, only rare alleles (A30, B7 0) remain significantly different from the controls al:ter correction of th e p value. No distorsion of the Mendelian sharing of haplotypes was observe d among sibling pairs of familial nonagenarians. A protective effect of the HLA-DR11 molecule itself, presenting adequately immunogenic - infectious peptides, is probable rather than genes in disequi librium. Our study strongly supports the heterogeneity of longevity, the association of HLA-DR11 in its familial form in aged populations.