The association between human leucocyte antigens (HLA) and mortality in community residents aged 85 and older

OBJECTIVE: The association between Human Leucocyte Antigens (HLA) and aging was investigated. It is possible that HLA antigens are associated with longevity, either indirectly through disease associations or directly through involvement in the aging mechanism. DESIGN: Community-based follow-up study. SETTING: Leiden, the Netherlands. PARTICIPANTS: A total of 919 subjects were HLA typed in this community-based study. All subjects were aged 85 and older and were white. Seventy-two percent of the cohort was female. MEASUREMENTS: Age- and sex-adjusted Mortality Rate Ratios (MRR) were estimated for 79 antigens by the subject-years method. HLA-A, -B and -C typing was performed with the standard NIH lymphocytotoxicity test, HLA-DR and -DQ typing was performed with the two-color fluorescence test. Homozygosity for HLA-A, -B, and -DR was defined as only one detectable antigen at a locus. RESULTS: The mean follow-up period (SD) was 5.0 (0.6) years. At the end of the follow-up, 70% of the subjects had died. The MRR (95%CI) for B60 was 0.96 (0.75-1.23), and for DR11 it was 0.82 (0.66-1.01). For A2 and A26 only, the MRR (95%CI) was significantly different from 1: 0.85 (0.73-0.99), P = .04 and 1.45 (1.06-1.99), P = .02, respectively (P values not corrected for the number of antigens tested). Homozygosity was not associated with mortality. CONCLUSIONS: HLA was not associated with mortality after the age of 85. Therefore, direct involvement of HLA in aging is unlikely. We suggest that the findings of previous studies are attributable to methodological shortcomings such as small sample size and differences in genetic background of the subjects.