[Okinawa Longevity Study. Molecular genetic analysis of HLA genes in the very old]

We analyzed HLA class II genes of Okinawan centenarians using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to identify primary genetic factors in the major histo-compatibility complex (MHC) region associated with human longevity. Gene frequencies of centenarians were compared with those of normal adults of the same ethnicity who were selected in the same vicinity as the centenarians. The following differences were identified in the HLA-DQB1 and DQA1 genes: the frequencies of DQB1*0503, DQA1*0101 (04) and DQA1*05 were increased in the centenarians, whereas those of DQA1*0102, DQA1*0103 and DQB1*0604 were decreased. Similarly, for the DRB1 gene, the frequencies of DRB1*0101, DRB1*1201 and DRB1*1401 were increased in the centenarians, whereas those of DRB1*0403 and DRB1*1302 were decreased. These data suggest that several alleles of the HLA-DRB1 and/or HLA-DQ genes are involved in human longevity.