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OBJECTIVE: To determine the association between cyclooxygenase-2 (COX-2) genotypes and risk and severity of rheumatoid arthritis (RA) in a Korean population. METHODS: A total of 258 Korean patients with RA and 400 control subjects were recruited from Hanyang University Hospital. Subjects were genotyped for the -765G/C polymorphism of the COX-2 gene by RFLP-PCR analysis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to estimate risk. Severity of RA was assessed by anatomical stage according to Steinbrocker, et al. RESULTS: No association was observed between COX-2 genotype and risk or severity of RA. However, among those without the shared epitope (SE), carriers of the low activity C allele had a lower risk of RA and less severe form of RA than subjects with the G/G genotype. The OR (95% CI) was 0.36 (0.14-0.95) for risk of RA and 0.04 (0.01-0.41) for severity. CONCLUSION: These results suggest that COX-2 genotyping might be useful in predicting the risk and severity of RA in individuals without the SE.