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TABLE I-HLA-DR AND DQ ANTIGEN FREQUENCIES IN 82 CENTENARIANS AND 159 OTHER ADULTS IN OKINAWA

~ 43% 19 3813 20 8220$ 30 8 at of 2834 30 af& eee - 4So) Lo “40 S )60“EV18-29 30-49 50-59 60-63 70-79 5-68 90~99 100-106Age {years) blank159 control18 ~85,%-20OR1

        HLA Adult aged Centenarianantigen n (PF) n (PF) p Pe RRDRI 010) 5 (6-1) a 0-00420 | 0 12597 | 12-3DR2 66 (41-5) 38 (46-3) ..DR3 010) 2(24)DR4 73 (45 9) 42 (51-2)DRS5 32 (20-1) 11 (13-4)DRw6 36 (22-6) 17 (20-7)DR7 0/0) 0/0)DRw8 39 (24-5) 20 (24-4) a - -DRw9 49 (308) 7(85) 0 00004 | 000129 | 48DRw10 0 (0) 4 (4-9) 0-01276 | 0-38277 | 10-1DRw11 (5) 8 (5-0) 5 (61) aeDRwI2 (5) 24 (15-1) 6 (7-3)DRw13 (6) 22 (13-8) 8 (9-8)DRw14 (6) 14 (8-8) 4 (4-9)DR blank 23 (14-5) 18 (22:0}DRw52 90 (56-6) 42 (51-2)DRw53 108 (67-9) 50 (61-0)Dow! 111 (69-8) 60 (73-2)DQw2 00) 2 (2-4) we oe .:135 (84-9) 56 (68-3) —0-00258 | 0:03092 | 2:6DQw3 

Distribution of phenotype frequencies for HLA-DR1 and DRw9 in Okinawan-Japanese.

*: number of subjects. p. values against control:

yr S DR

: p =

, RR =

,

, DRw

: p=

-

, RR-

;

yr S DR

: p =

-

, RR=

-

, DRw

: pc=

,RR=

Blank includes undefined specificities and homozygotes for HLA-DR antigens.

PF=phenotype frequency (%); p values for <0-05 shown; minus sign indicates negative association.

but also nonagenarians (see accompanying figure). among RR and pc were higher when age 90 instead of age 100 was taken the cut-off point for comparison of phenotype as frequencies (figure, footnote). However, significant no difference was found between subjects in an age-group for the normal adults.

HLA Typing

Sixty-one specificities on HLA-A, B, C locus and nineteen on DR, DQ locus were targeted and typed according to standard microdroplet lymphocyte cytotoxicity testll using sera by Dr P. 1. Terasaki, University of California Los and those of the 8th and the 9th International Workshop. In of blanks (ie, unspecified cases type and homozygotes) or difficulties with antigen additional antisera were employed, and, as much as samples were re-typed to ensure accuracy and to minimise error.

Discussion

A clear-cut relation between the H-2 system and maximum lifespan3 and highly strain-dependent, a age- specific incidence of certain diseases, including have malignancies,15 been demonstrated in mice, but the relation between HLA and longevity has never been clear in However, in Orientals, and especially in Japanese, man. most autoimmune diseases are related to HLA-DRw9

Data Analysis

Fisher’s exact probability test was used for the statistical analysis, correction for number of antigens and was two-tailed. Relative (RR) was also calculated and its significance was measured by X2 a simple 2 x 2 table. 12 For the analysis subjects’ ages were taken age at time of collection of final blood samples or age when subject confirmed to be alive.

TABLE II-VARIOUS DISEASE ASSOCIATION OF HLA-DRI AND DRW9 IN ORIENTAL POPULATION

Results

The centenarians had extremely low phenotype an frequency (PF) of HLA-DRw9 (PF=8-5%; 7/82) when compared with normal adults (308%; 49/159) (table 1). For Okinawan-Japanese, the chances of living beyond 100 years thus 4-8 times higher for those without than for those are with DRw9 (ie, RR 4-8, corrected p [pc] 0-0013). DRw9- B40 (Bw60/w61), commonly found in most Japanese, also occurred infrequently in centenarians (data not shown;