Homozygous MHC Genotypes and Longevity

• Published in: Human heredity 1994-09, Vol.44 (5), p.271-278
• Main Authors: Dorak, M. Tevfik, Mills, Ken I., Gaffney, Dairena, Wilson, David W.L., Galbraith, Ian, Henderson, Nancy, Burnett, Alan K.
• Format: Article
• Language: English
• Subjects: Adult; Age Factors; Aged; Alleles; Biological and medical sciences; Classical genetics, quantitative genetics, hybrids; Female; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genetics of eukaryotes. Biological and molecular evolution; HLA-DQ alpha-Chains; HLA-DQ Antigens - genetics; Homozygote; Human; Humans; Longevity - genetics; Major Histocompatibility Complex - genetics; Male; Middle Aged; Original Paper
• ISSN: 0001-5652; 1423-0062
• DOI: 10.1159/000154229

To investigate the relevance of the major histocompatibility complex (MHC) in longevity, we carried out a molecular analysis of the MHC in 432 unrelated healthy individuals. The comparison of individuals ≤25 years and >25 years showed that the 5.8-kb DQA1 allele, which corresponds to HLA-DR53, was negatively associated with longevity (p = 0.0035) resulting mainly from decreased homozygosity with age for that allele (p = 0.008), and restricted to males (p = 0.008). The difference was more striking for the 5.8 kb DQA1: 9.0 kb HSP70 haplotype again only in males (26.3 vs. 6.2%; p = 0.017, OR = 5.4, 95% CI = 1.5-19.5). The oldest male subject homozygous for this DQA1: HSP70 haplotype was 54 years (p = 0.005). Comparing leukemic patients and healthy individuals with the same ethnic and geographical origin, homozygosity for these genotypes was more frequent in the young leukemic group. The results suggested the existence of recessive deleterious genes in a segment of HLA-DR53 haplotypes.