Human leucocyte antigens (class I and II) in central Taiwan aborigines: can these explain the observed differences in rheumatic disease patterns compared with Han Chinese?

C. T. Chou and H. R. Schumacher1

Division of Allergy–Immunology–Rheumatology, Department of Medicine, Veterans General Hospital, Taipei, Taiwan and
1 University of Pennsylvania and Arthritis–Immunology Center, Department of Veterans Affairs Medical Center, Philadelphia, USA

SIR, The population of Taiwan includes four ethnic groups. The major inhabitants are Taiwanese, whose ancestors migrated from the Fukin province 400 yr ago. Taiwanese and other island residents (including Hakka, who originally moved from Guangdong province, and Mainlanders, who moved from Mainland China after World War II) are Han and Mongoloid people. An important minority is the aborigines, who were the early settlers of the island. The ancient aborigines in Taiwan probably moved from Southeast Asia and then migrated from Taiwan to western and central Polynesia and New Zealand [1]. Gout is a common rheumatic disease in Taiwan aborigines. A previous study of this population showed that hyperuricaemia and gout were common in Taiwan aborigines, and the estimated prevalences of the two diseases were 11.7 and 41.4% respectively [2]. In contrast, rheumatoid arthritis (RA) and ankylosing spondylitis (AS) were uncommon in aborigines compared with Han people. In a preliminary study by Chou et al. [3], the prevalence of RA was 0.6% and that of AS was 0.3% in Han Chinese; in aborigines the combined prevalence of the two diseases was less than 0.05% [more than 2000 aborigines were investigated, but none was confirmed to have either RA or AS (unpublished results)]. In the present study, antigenic specificities of the class I loci HLA-A, HLA-B and the class II locus HLA-DR were determined simultaneously in aborigines and Taiwan Chinese (Han people) in order to understand the immunogenetic differences between the two groups and the relationship between the prevalent rheumatic diseases and HLA genes in aborigines.

Heparinized blood samples from 167 Taiwan aborigines and 110 Han Chinese were sent immediately to the Chinese Blood Services Foundation, Taipei, for typing of HLA-A and HLA-B (class I) antigens. HLA-DR (DRB1) types were determined by the oligotyping technique. The antigen frequency for each HLA-A and B allele was calculated.

The two most frequent HLA-A alleles in aborigines were A24 (81.4%) and A2 (38.3%), whereas in Han Chinese the most frequent were A11 (64.5%) and A2 (39.1%) (Table 1Go). For the HLA-B locus, the two most frequent alleles in aborigines were B60 (56.3%) and B55 (26.2%), whereas in Han they were B46 (32.7%) and B60 (31.8%). At the HLA-DR locus, DR14 and DR8 were the two most common alleles in aborigines (60.5 and 34.9% respectively), in contrast to DR9 and DR12 in Han people (22.3 and 20.2% respectively). Statistical analysis showed that DR8 and DR14 were significantly more frequent in aborigines than in Han, whereas DR7, DR13, DR15 and DR17 were significantly less frequent in aborigines than in Han people.


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TABLE 1. Frequencies of antigenic specificities of the HLA-A and HLA-B loci in 167 aborigines and 110 Han Chinese in Taiwan

 
It is clearly demonstrated that class I (HLA-A, HLA-B) and class II (DR) genes showed a significant variation between Taiwan aborigines and Han people. At the HLA-A locus, the frequency of A24 was much higher in aborigines than in Han people (81.4 vs 36.4%, P < 0.001). This result is very similar to those of Lin et al. [4] and Lee et al. [5], who showed that 81% of Bunon aborigines and 97% of either Paiwan or Rukai aborigines had A24, but their case numbers were small. Like the Taiwan aborigines, the Oceanic population, including Papua New Guinean, Javanese, Timorese and Maori people, also had a high prevalence of A24 [6]. The frequency of A11 in Taiwan Chinese (Han) was much higher than in Taiwan aborigines and other minority peoples, including Javanese, Timorese and Maori people.

In Atayal aborigines, the most common B antigen of the HLA-B locus was B60, which was present at a significantly higher frequency than in Han people (56.3 vs 31.8%, P < 0.001). However, this result was not significantly different from that in the study of Lin et al. [4], who found a frequency of 32.7% in Atayal, 20.7% in Bunon and 19.7% in Rukai aborigines. In the present study, DR14 and DR8 were the two most common antigens in Atayal aborigines. This is in contrast to the report by Kobayashi et al. [7], who showed that either DR2 (now split into DR15 and DR16) or DR4 was predominant in five tribes, but their total number of individuals from the five tribes was only 39.

A preliminary study by Chou et al. [3] showed that the prevalence of RA in three areas of Taiwan was 0.26, 0.78 and 0.93%. This was much higher than in the aborigines (<0.05%). As in most Western reports, the frequency of HLA-DR4 was also significantly increased in Han patients with RA [8]. In the present study, the frequency of DR4 was similar in Han people and aborigines but the prevalence of RA differed greatly between these two groups. The high prevalence of gout and the low prevalence of RA in this study is similar to a previous finding in Maoris (22 of 462 had gout but none had definite RA) [9]. This implies that there may be genes other than DR4 that increase the frequency of gout but decrease that of RA. Further studies including MICA (major histocompatibility complex class I-related chain gene A) and non-HLA genes are indicated. The frequency of the antigen B27 did not differ significantly between aborigines and Han people (6.0 vs 6.4%, P > 0.05) (Table 1Go), but the prevalence of AS is lower in aborigines than in Han. Our laboratory recently found a point mutation [one amino acid difference in the {alpha}1 domain position 70 or 63 (C. T. Chou, unpublished results)] in the B2704 antigen in a group of aborigines positive for B27. Whether the lower prevalence of AS in the aborigines compared with Han Chinese is due to a difference in B27 subtype [10] or to environmental factors remains to be answered.

Notes

Correspondence to: C. T. Chou, Division of Allergy–Immunology–Rheumatology, Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Shih-Pai, Taipei, Taiwan 11217. Back

References

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  7. Kobayashi K, Ato M, Suzuki H et al. A study of HLA distribution among Taiwan aborigines. In: Tsuji K, Aizawa M, Sasazuki T, eds. HLA 1991, Vol. 1. New York: Oxford University Press, 1992:679–80.
  8. Chou CT, Chang DM, Ho YS, Lee CF, Leu FJ. Subcutaneous nodules in Chinese patients with rheumatoid arthritis. J Med Sci ROC1987;86:829–32.
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Accepted 2 May 2000





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