frequencies of HLA-OR81 alleles

Centenarians Normal adults (n=120) (nP129) OR81 n GF(%) PF (Yo) n GF (Yo) PF (96) P Pc RR 0101 12 5.0 5.4 3 1.2 1.3 0.016 0.408 4.300 1501 25 10.4 10.3 35 13.6 13.9 0.335 1502 15 6.3 6.3 13 5.0 4.9 0.567 1602 3 1.3 1.3 2 0.8 0.9 0.676 0302 2 0.8 0.9 2 0.8 0.9 1. ooo 0401 9 3.8 3.6 9 3.5 3.1 1.000 0403 9 3.8 4.0 23 8.9 9.4 0.027 0.670 0.421 0405 46 19.2 17.4 65 25.2 22.9 0.131 0406 9 3.8 3.6 6 2.3 2.7 0.435 0407 4 1.7 1.8 3 1.2 1.3 0.716 041 0 7 2.9 3.1 7 2.7 3.1 1.000 1101 13 5.4 5.8 7 2.7 3.1 0.170 1102 2 0.8 0.9 0 0.0 0.0 0.500 1201 7 2.9 2.7 1 0.4 0.4 0.032 0.829 7.525 1202 4 1.7 1.8 2 0.8 0.9 0.435 1301 1 0.4 0.4 4 1.6 1.8 0.374 1302 3 1.3 1.3 15 5.8 5.8 0.007 0.1 87 0.21 5 1401 27 11.3 11.6 7 2.7 2.7 0.0002 0.004 4.146 1402 1 0.4 0.4 1 0.4 0.4 1. ooo 1405 3 1.3 1.3 1 0.4 0.4 0.356 1406 5 2.1 2.2 1 0.4 0.4 0.111 0701 0 0.0. 0.0 1 0.4 0.4 1. om 0802 7 2.9 3.1 3 1.2 1.3 0.208 0803 6 2.5 2.2 13 5.0 5.4 0.164 0901 20 8.3 8.5 34 13.2 12.1 0.086

PF (YO):p henotype frequency; GF (%): oenotype frequency: k? Plevel by Fisher's exact probability test for GF; Pc: corrected P: RR: relative risk.

 

Gene frequencies of HLA-DOB1

Centenarians Normal adults (n=120) (n=129) DOE1 n GF (%) PF (%) n GF (%) PF(%) P pc RR 0201 1 0.4 0.5 2 0.8 0.9 1.000 0301 53 22.1 21.3 47 18.2 17.4 0.314 0302 12 5.0 5.1 21 8.1 9.4 0.207 0303 18 7.5 7.4 21 8.1 7.0 0.868 0401 46 19.2 18.5 52 20.2 19.2 0.822 0402 10 4.2 4.6 12 4.7 5.2 0.831 0501 4 1.7 1.9 6 2.3 2.3 0.753 0502 1 0.4 0.5 3 1.2 1.4 0.624 0503 29 12.1 13.0 6 2.3 2.8 0.00002 0.0002 5.196 0504 1 0.4 0.5 0 0.0 0.0 1. ooo 0601 22 9.2 8.8 28 10.9 10.8 0.554 0602 33 13.8 13.4 37 14.3 13.6 0.898 0603 1 0.4 0.5 3 1.2 1.4 0.624 0604 4 1.7 1.9 13 5.0 5.2 0.048 0.7155 0.331 0605 5 2.1 2.3 7 2.7 3.3 0.773

PF (%): phenotype frequency: GF (YO):g enotype frequency; P P-level by Fisher's exact probability test for GF: Pc: corrected P; RR: relative risk.

of DQB1*0503 (x2=16.66, P=0.00002, Pc= 0.0002, RR=5.196) was significantly higher in the Okinawan centenarians than in the normal adults and other alleles did not significantly increase or decreased after the corrected P value test (Table 2). Moreover, as listed in Table 3, the frequencies of DQA1*0101=0104 (x2=7.38, P=0.005, P,=0.040, RR=1.739) and DQA1*05 (x2=7.36, P=0.005, P, =0 .038 , RR =2 .508) were significantly higher, whereas those of DQAl*O102 (x2=4.85, P=0.026, RR=0.551) and DQA1*0103 (x2=3.63, P=0.047, RR=0.518) were lower in the Okinawan centen- arians as compared with the normal adults. The negative association with DQA1*0102 or with DQAl*0103 did not reach statistical significance when the P value was corrected by the number of comparisons made. When the correction with the number of all class I1 markers for each marker was

Results

The allelic distributions of the DRB1, DQBl and DQAl genes in the centenarians and normal adults in the Okinawa islands are summarized in Tables 1, 2 and 3, respectively.

As to the DRB1 gene, the frequencies of (x2 DRB 1* O 101 = 5.02, P=O.O 16, RR=4.300), DRB1*1201 (~"3.56, P=0.032, RR=7.525) and (x2= DRB1*1401 12.93, P=0.0002, Pc=0.004, RR=4.146) were increased, whereas those of DRB1*0403 (x2=4.69, P=0.027, RR=0.421) and DRB1*1302 (x2=6.18, P=0.007, RR=0.215) were decreased in the Okinawan centenarians as com- pared with the normal adults (Table 1). Among them only a positive association with DRB1*1401 was statistically significant even after the corrected P value test (P,).A t the DQBl locus the frequency

 

Gene frequencies of HIA-DOA1 alleles

Centenarians Normal adults (n= 120) (n=129) DOAl n GF(%) PF(Yo) n GF (Yo) PF (Yo) P pc RR 0101=0104 55 22.9 24.4 34 13.2 15.0 0.005 0.040 1.739 010 2 20 8.3 9.3 39 15.1 18.2 0.026 0.206 0.551 010 3 13 5.4 5.7 27 10.5 12.1 0.047 0.377 0.518 0201 0 0.0 0.0 1 0.4 0.5 1.000 03 116 48.3 43.0 137 53.1 44.9 0.324 0401 6 2.5 3.1 5 1.9 2.3 0.765 05 28 11.7 13.5 12 4.7 5.6 0.005 0.038 2.508 .o 0601 2 0.8 1 3 1.2 1.4 1.000

PF (YO):p henotype frequency: GF (%): genotype frequency: P: P-level by Fisher's exact probability test for GF: P,: corrected P; RR: relative risk.

centenarians (1 1.3%) and higher than that of the controls (2.7%) in the Okinawa islands in the pres- ent study. The frequencies of other HLA class I1 alleles in the normal adults in the Okinawa islands were similar to those in Japanese (16). Further, al- lelic distribution for HLA class I1 genes in a south- eastern Chinese population, for example, in Shanghai Chinese (17) was different from those of Okinawan centenarians but relatively close to those of Okinawan controls investigated in this study, especially on the alleles of DRBl*1401, DQB1*0503 and DQA1*0101=0104, excluding the possibility that significant associations with HLA class I1 alleles in Okinawan centenarians simply reflects a characteristic of a specific ethnic population such as southern Chinese who immi-

done, only the deviations for DRB1*1401 and DQB 1* 0503 remained significant.

Discussion

Although a few reports have focused on HLA anti- gens in association with longevity (1 1, 12), they adopted only serological typing. As for the Ja- panese subjects, it was reported that DR1 was sig- nificantly high in the Okinawan centenarians, in contrast to the low incidence of DR9 (12). This was the first report on HLA class I1 serological typing of centenarians.