為了探討HLA-DQA1基因及其和HLA-DRB1間的交互作用,在台灣地區類風濕性關節炎病人的致病機轉中所扮演的角色。我們選擇了71個RA病人和108個正常人,利用SSP-PCR方法測定其HLA-DQA1基因型。其中,同時有55個RA病人和101個正常人利用PCR/SSOP方法檢測其HLA-DRB1,而HLA-DR4的亞型則是利用選殖定序法測定。類風濕性關節炎病人具有HLA-DQA1*0301的機會比正常人顯著減少,而具有HLA-DQA1*0302或DQA1*0303的機會則比正常人顯著增高。而且,DQA1*0301、*0302、*0303和RA間的關係與HLA-DR4、DRB1*0405無關。再者,HLA-DR4和HLA-DQA1*0302或DQA1*0303同時出現時更可加強它們和RA間的關係。吾人同時發現HLA-DQA1*0303陽性的RA病人比陰性者發生骨骼糜爛和出現類風濕因子的機會顯著增加。HLA-DQA1*0302和DQA1*0303是發生類風濕性關節炎的危險因子而DQA1*0301則是保護因子。同時具有HLA-DR4和DQA1*0302或DQA1*0303對該病的發生有加成作用。而且,HLA-DQA1*0303和骨骼糜爛以及類風濕因子的出現有關。
To investigate the role of HLA-DQA1 genotypes and their interaction with HLA-DRB1 in the pathogenesis of rheumatoid arthritis (RA) in Taiwan, HLA-DQA1 was determined in 71 patients with RA and 108 healthy controls by SSP-PCR method. HLA-DRB1 and HLA-DQA1 were simultaneously detected in 55 RA patients and 101 healthy controls. PCR/SSOP method was used to determine the HLA-DRB1 genotypes, and the subtypes of HLA-DR4 were determined by cloning and sequencing. The phenotypic frequency of HLA-DQA1*0301 was significantly lower in RA than in controls, and, in contrast, the HLA-DQA1*0302 and DQA1*0303 were significantly higher in RA than in controls. The associations of DQA1*0301, *0302, and *0303 with RA were independent of DR4 and DRB1*0405. Moreover, the interactions between HLA-DR4 and HLA-DQA1*0302 or DQA1*0303 could enhance the development of RA. We also found that the prevalence of bone erosion and seropositivity of rheumatoid factor (RF) were significantly higher in HLA-DQA1*0303 positive RA patients than in healthy controls. HLA-DQA1*0302 and DQA1*0303 are the risk factors for susceptibility to RA, while HLA-DQA1*0301 is a protective factor. A synergistic effect for the susceptibility to RA can be found between HLA-DR4 and HLA-DQA1*0302 or DQA1*0303. We also found that the HLA-DQA1*0303 was related to bone erosion and seropositivity of RF in RA patients.