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HLA‐B27 and other related genes in ankylosing spondylitis in APLAR countries

2005; Wiley; Volume: 8; Issue: 3 Linguagem: Inglês

10.1111/j.1479-8077.2005.00159.x

1479-8077

Chung‐Tei Chou,

Dermatology and Skin Diseases

Ankylosing spondylitis (AS) is a seronegative spondyloarthropathy (SPA) that mainly affects axial and peripheral joints, uvea and enthesis, and so on.1 The relationship between B27 and AS was found by a British investigator in 19732 which considerably differentiated this disease from rheumatoid arthritis (RA). In the last three decades, many studies on HLA-B27 and other genes in AS or other SPAs has been done. Although it is a trend that the prevalence of HLA-B27 is increasing in the northern hemisphere and declining in the southern hemisphere, different ethnic groups may present a variable finding.3,4 Among Asian countries, a very low prevalence of B27 was demonstrated in Japanese (1%) when compared to other Asian people. In Chinese subjects, the frequency of HLA-B27 in the general population is reportedly from 4% to 8%.5,6 The prevalence of HLA-B27 in Chinese patients with AS is about 95%, which is similar to that in Caucasians. Tibetans in China showed a higher prevalence of HLA-B27 (12%) in comparison with Han Chinese. The different aboriginal peoples living in Taiwan, in general, have a relatively lower prevalence of HLA-B27 (0–2.1%), except for the Atayal tribe.6 The findings are similar to the results among Polynesians in the South Pacific region (0–3%). It is suggested that most indigenous tribes in Taiwan are believed to be closely related to the population in Oceania.6,7 The B27 antigen frequency among South-East Asians, including Vietnamese, Thais, Filipinos, Malaysians and Indonesians range from 5% to 12%, which is close to or higher than in the Chinese population. Historically, at least part of the South-East Asian ancestry immigrated from the southern regions of China. Even now, 40% of Malaysians and 90% of Singaporeans are still of Chinese origin. That may be one of the reasons why B27 frequency is so close between Chinese and other ethnic groups living in South-East Asian countries. One interesting finding in Indonesia is a relatively higher prevalence of B27 (5–12%) in native Indonesians but with a lower prevalence of AS; this is contrary to the Chinese population in Indonesia.3,8 It has been concluded that Indonesia is thus far the only country in which SPA is not associated with HLA-B27. Examining the HLA-B27 frequency among Atlantic linguistic groups revealed variably in different groups. It is much higher in Siberian Chukchis and SiberiansYakalts (17–34%). Other ethnic groups including Koreans, Mongolians and Turkic had a similar prevalence (3–9%) of B27 as Chinese, except for Japanese (≤ 1%). B2704 is the predominate subtype in both the general population (85%) of Taiwanese (majority are Han Chinese) or patients with AS (93.9%). The second common subtype was B2705 in Chinese and AS patients (14.9% and 6.1%, respectively).6 In Taiwan aborigines, B2704 is the only subtypes in people with or without AS. The similar frequency of the B2704 subtype between aborigines and Han Chinese suggests aborigines are a unique population and may originate from an Asian country. In general, B2705 and B2704 are the major subtypes in Asian people. B2705 is the predominant subtype in Indians, Koreans and Polynesians. B2704 was found more frequently in Japanese, Chinese and Thais. However, B2706 is the predominant subtype among native Indonesians. The relationship between the prevalence of these subtypes and AS in Asians has not been demonstrated.9 Limited numbers of AS and controls in Thai, including 45 B27 positive AS patients and 17 controls, showed B2706 was absent among AS patients but present in 47% of controls. Therefore, B2706 may serve as a 'protective gene' for AS in Thai people. But this requires confirmation by expanding to large sample sizes in both AS patients and controls. Whether B2706 in native Indonesians influences the result of low prevalence of AS but high prevalence of B27 in native Indonesians when compared to the local Chinese, still remains unclear. Since B27 confers the greatest possibility for AS, studies on B27-negative AS may reveal other MHC genes as developing AS. In Caucasians, Robinson and Brown reported that HLA-B60 increased the risk of developing AS in both B27 positive and negative individuals.10,11 Early studies showed that B7 and B16 were associated with B27 negative Caucasian AS patients.12,13 In Asia, Yamagachi demonstrated the association of B39 with HLA-B27 negative Japanese AS patients.14 Wei and Chou studied 41 B27-negative Taiwanese (Han Chinese) AS patients and found both B60 and B61 significantly increased susceptibility to AS in HLA-B27 negative patients.15 To locate and enlist large numbers of B27 negative AS patients in each Asian country is difficult. However, it is interesting to realize beyond B27, how many other MHC genes may be involved in the pathogenesis of AS in the different ethnic groups of Asia. When patients share features of SPA but do not carry typical clinical features which can be diagnosed either as AS, reactive arthritis, psoriatic arthritis or inflammatory bowel disease, they are recognized as USPA.16,17 To address whether familial and sporadic USPA are identical diseases, including the prevalence of B27, we enrolled 21 USPA people from 102 with AS in family relatives and 22 USPA without either AS or USPA in relatives.17 There was no significant difference in clinical features in these two groups. However, when the percentages of HLA-B27 were compared, they were 100% in the familial group but only 50% in the sporadic group (P < 0.001). In this family study, we concluded that both USPA and AS are predisposed by HLA-B27. However, a significant subset of sporadic USPA has a different genetic predisposition compared with familial USPA. Asian countries involve a huge and heterogenous population. Therefore, studies on the epidemiology of B27 and AS in many countries is necessary. Besides B27, investigation of other MHC genes or non-MHC genes in AS or SPA, may provide an insight into which candidate or susceptibility gene may predispose Asia's diverse ethnic groups to AS.