Izaks G J, van Houwelingen H C, Schreuder G M, Ligthart G J
Section of Gerontology, Leiden University, The Netherlands.
J Am Geriatr Soc. 1997 Jan;45(1):56-60. doi: 10.1111/j.1532-5415.1997.tb00978.x.
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.
Community-based follow-up study.
Leiden, the Netherlands.
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.
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.
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.
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.
研究人类白细胞抗原（HLA）与衰老之间的关联。HLA抗原有可能通过与疾病的关联间接或通过参与衰老机制直接与长寿相关。
基于社区的随访研究。
荷兰莱顿。
在这项基于社区的研究中，共有919名受试者进行了HLA分型。所有受试者年龄均在85岁及以上，且为白人。该队列中72%为女性。
采用受试者年数法估计了79种抗原的年龄和性别调整死亡率比（MRR）。HLA - A、- B和 - C分型采用标准的美国国立卫生研究院淋巴细胞毒性试验，HLA - DR和 - DQ分型采用双色荧光试验。HLA - A、- B和 - DR的纯合性定义为在一个位点上仅检测到一种抗原。
平均随访期（标准差）为5.0（0.6）年。随访结束时，70%的受试者死亡。B60的MRR（95%置信区间）为0.96（0.75 - 1.23），DR11的MRR为0.82（0.66 - 1.01）。仅对于A2和A26，MRR（95%置信区间）与1显著不同：分别为0.85（0.73 - 0.99），P = 0.04和1.45（1.06 - 1.99），P = 0.02（P值未针对所检测抗原的数量进行校正）。纯合性与死亡率无关。
85岁以后HLA与死亡率无关。因此，HLA直接参与衰老的可能性不大。我们认为先前研究的结果归因于方法学上的缺陷，如样本量小和受试者遗传背景的差异。
