The summary ORs showed that Asian-Mongoloid patients with RA had significantly higher frequencies of HLA-DRB1* 0101, *0401, *0410, and *1001 than controls (OR 1.5-2.1, p<0.05 for association). The results of meta-analysis are summarized in Table 2, 3. Finally, the trim and fill method was used to adjust for publication bias ( 18). Publication bias was assessed graphically by funnel plot ( 15) and was statistically evaluated by the regression asymmetry test ( 16), which has been shown to be a powerful test for assessment of publication bias ( 17).
Considering the low power of the Q statistic, the heterogeneity test was considered significant when the p value was less than 0.1 ( 14). For the Mantel-Haenszel method, the test for heterogeneity is based on the weights from the inverse-variance method ( 13). Summary ORs were computed using fixed effects models of the Mantel-Haenszel method ( 13), and the heterogeneity of the study results was evaluated with chi-square-based Q statistics.
Differences in results may be related to the ethnic and clinical heterogeneity of the patients studied or to the relatively small numbers of patients in each study.Ĭomparisons of allele frequencies between patients and controls were made using the Z test ( 13) and summary odds ratios (ORs) with 95% confidence intervals (CIs). Many studies have attempted to clarify this relationship, but there has been no definite consensus to date ( 4). The shared epitope (SE) hypothesis has been proposed to explain susceptibility to RA, based on the observation that HLA-DR specificities associated with the disease share a similar amino acid sequence in the third hypervariable region of the HLA-DRB1 molecule ( 2, 3).
Genetic variation is believed to be important in determining both the susceptibility to and severity of RA, with the strongest association being observed in the HLA region, in particular, with HLA-DRB1 alleles ( 1). The prevalence of RA is about 1% of the population worldwide, and genetic factors have been estimated to account for 60% of the disease risk ( 1). Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the joints, which may lead to joint destruction and disability. Keywords: Arthritis, Rheumatoid, Genetics, Epitopes, HLA-DRB1, Meta-analysis, Asian Continental Ancestry Group All the RA-associated alleles except DRB1*0301 could be explained by the structural model supporting the SE hypothesis that RA susceptibility is determined by the combination of amino acid residues at HLA-DR β71 and β74, not by β71 alone. When analyses were restricted to more ethnically homogeneous populations, HLA-DRB1*0405 showed a significant susceptibility to RA in Koreans (OR 5.65, 95% CI 4.32-7.39), whereas the HLA-DRB1*0301, *0403, *0406, *0701, *1301, and *1405 alleles showed protective association with RA (OR 0.32-0.70, p<0.05 for association). Mongoloid-Asian patients with RA had significantly higher frequencies of HLA-DRB1*0101, *0401, *0410, and *1001 than controls (OR 1.5-2.1, p<0.05 for association). Among the papers published between January 1987 and July 2006 on RA susceptibility in Asian-Mongoloid populations (Korean, Japanese, Chinese, and Thai), 12 were selected for the meta-analysis. The aims of this study were to summarize results on the association of HLA-DRB1 with rheumatoid arthritis (RA) in Asians and to determine if the shared epitope (SE) hypothesis could explain the meta-analysis results.