title: Association between the HLA-DR alleles and longevity: a study in Sardinian population.
abstract: Human longevity may be correlated with optimal functioning of the immune system, suggesting that genetic determinants of longevity also resides in those polymorphisms for the immune system genes that regulate immune responses as histocompatibility (HLA) antigens. However, conflicting results have been obtained. Some well planned and designed association studies performed in Caucasians suggest that longevity is associated with positive selection of alleles (i.e. HLA-DR11) or haplotypes (i.e. HLA-B8,DR3) that confer resistance to infectious diseases, respectively, via peptide presentation or via antigen non-specific control of immune response. Association studies are subjected to a number of possible confounding factors, the homogeneity of the population in term of geographical origin among others. Because of the lack of large-scale heterogeneity, the Sardinians represent a suitable population for association studies addressed to dissect the complex traits as longevity. Thus, we have evaluated, by the amplification refractory mutation system/polymerase chain reaction, HLA-DR frequencies in 120 centenarians (79 women and 41 men) and 86 controls (53 women and 33 men) from Sardinia, to validate, in this very homogeneous population, the associations between HLA alleles or haplotypes and longevity observed in other Caucasoid populations. No significant differences were obtained by analysing the differences between Centenarians and controls except for HLA-DRB1*15 that was increased in centenarians. However, the significance was not maintained by multiplying P values for the number of alleles under study. Thus, in Sardinian centenarians, we were not able to confirm the findings observed in the well planned and designed studies performed in other Caucasoid populations. Besides, HLA HFE gene polymorphisms have been recently demonstrated to be associated with longevity in the Sicilian population but not in Danish one. On the whole these findings clearly show that HLA/longevity associations are population-specific, being heavily affected by the population-specific genetic and environmental history. So, in our opinion, HLA genes might be considered survival genes not longevity genes.
authors.affiliation: Gruppo di Studio sulll'Immunosenescenza, Laboratorio di Imunopatologia, Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, Corso Tukory 211, 90134 Palermo, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Lio
authors.forename: Giovanni Mario
authors.initials: GM
authors.lastname: Pes
authors.forename: Ciriaco
authors.initials: C
authors.lastname: Carru
authors.forename: Florinda
authors.initials: F
authors.lastname: Listì
authors.forename: Viviana
authors.initials: V
authors.lastname: Ferlazzo
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Candore
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Colonna-Romano
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Luca
authors.initials: L
authors.lastname: Deiana
authors.forename: Giovannella
authors.initials: G
authors.lastname: Baggio
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.forename: Calogero
authors.initials: C
authors.lastname: Caruso
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D007558:Italy; D008136:Longevity / Q000235:genetics*; D008297:Male
chemical_list: D006684:HLA-DR Antigens