Familial versus sporadic longevity and MHC markers.
We have studied the polymorphism of HLA-A, B, in 2 elderly populations (> or = 90 years) compared to a control series of 429 healthy unrelated individuals less advanced in age. The aged population issued from the CHRONOS cohort consisted of 336 centenarians without familial history of longevity, and 102 nonagenarians index cases randomly selected from families. Almost all individuals (310) were previously typed for HLA-DRB1. The increased allelic frequency of HLA DR11 was observed in familial nonagenarians (18.3%) compared to controls (10%) (p < .001) and to sporadic centenarians (11.8%). Concerning HLA Class I alleles, only rare alleles (A30, B70) remain significantly different from the controls after correction of the p value. No distortion of the Mendelian sharing of haplotypes was observed 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 disequilibrium. Our study strongly supports the heterogeneity of longevity, the association of HLA-DR11 in its familial form in aged populations.
Henon
N
N
Jean Dausset Foundation, Paris, France.
Busson
M
M
Dehay-Martuchou
C
C
Charron
D
D
Hors
J
J
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008136:Longevity / Q000235:genetics* / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012737:Sex Factors
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens