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Cyclooxygenase-2 Polymorphisms and Risk of Rheumatoid Arthritis in Koreans
HYE-RYEON YUN, SOO-OK LEE, EUN JU CHOI, HYOUNG DOO SHIN, JAE-BUM JUN, and SANG-CHEOL BAE
ABSTRACT. Methods. Sequencing of the COX-2 gene using a DNA analyzer revealed genetic variants in 24 Korean DNA samples. A total of 1201 Korean patients with RA and 973 controls were genotyped using the TaqMan method. HLA-DRB1 was genotyped by polymerase chain reaction and sequence-specific oligonucleotide probe hybridization techniques. Logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) and the corresponding probability values for each SNP site and haplotype. Results. Direct sequencing identified 23 SNP of COX-2 gene, from which 2 common SNP (-1329A→G and 6365T→C) were selected based on the linkage disequilibrium status among SNP and minor allele frequencies. The -899G→C SNP was also studied because it is reportedly associated with the risk of RA. The -1329A→G SNP was not significantly associated with the risk of RA. However, the risk of RA was significantly lower in the presence of the C allele for 6365T→C (OR 0.50, 95% CI 0.29-0.85, in a recessive model, and OR 0.80, 95% CI 0.67-0.97, in a codominant model). The C allele for -899G→C was also associated with a significantly lower risk of RA (OR 0.67, 95% CI 0.48-0.95, in a codominant model). The radiologic severity of RA was not associated with COX-2 polymorphisms. Conclusion. Our study revealed a possible protective influence of the C allele for 6365T→C and for -899G→C in RA. (J Rheumatol First Release Mar 15 2008) Key Indexing Terms:
CYCLOOXYGENASE-2
From the Division of Rheumatology, Department of Internal Medicine, Hanyang University College of Medicine and the Hospital for Rheumatic Diseases, Hanyang University; and Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Korea. Supported in part by a grant of the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (01-PJ3-PG6-01GN11-0002). H-R. Yun, MD, Instructor, Division of Rheumatology, Department of Internal Medicine, Hanyang University College of Medicine and the Hospital for Rheumatic Diseases, Hanyang University; S-O. Lee, MS; E.J. Choi, BS; H.D. Shin, PhD, Department of Genetic Epidemiology, SNP Genetics, Inc.; J-B. Jun, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Hanyang University College of Medicine and the Hospital for Rheumatic Diseases, Hanyang University; S-C. Bae, MD, PhD, MPH, Professor, Division of Rheumatology, Department of Internal Medicine, Hanyang University College of Medicine, Director, the Hospital for Rheumatic Diseases, Hanyang University. Address reprint requests to Prof. S-C. Bae, Division of Rheumatology, Hospital for Rheumatic Diseases, Hanyang University Medical Center, Seoul 133-792, South Korea. E-mail: scbae@hanyang.ac.kr Accepted for publication November 29, 2007. |
