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Tumor Necrosis Factor-a Promoter –308 A/G Polymorphism and Rheumatoid Arthritis Susceptibility: A Metaanalysis
YOUNG HO LEE, JONG DAE JI, and GWAN GYU SONG ABSTRACT. Objective. Tumor necrosis factor-a (TNF-a) promoter –308 A/G polymorphism has been reported to be associated with rheumatoid arthritis (RA) with inconsistent results. We investigated whether TNF-a –308 A/G polymorphism confers susceptibility to RA. Methods. We conducted a random effect metaanalysis on the association of genotypes A/A (recessive effect), A/A + A/G (dominant effect), A allele, and A/A vs G/G genotypes of the TNF-a –308 polymorphisms with RA overall and within different ethnic populations. Results. Fourteen studies, 10 of Europeans, 3 of Latin Americans, and one Asian, were included in this metaanalysis. An association between RA and the TNF-a –308 A allele was not found in the overall population (OR 1.005, 95% CI 0.715–1.412, p = 0.976). However, stratification by ethnicity indicated that the TNF-a A allele was significantly associated with RA in Latin Americans (OR 2.004, 95% CI 1.158–3.467, p = 0.013). Conversely, there was no association detected for the TNF-a A allele with RA patients from the European samples (OR 0.911, 95% CI 0.684–1.212, p = 0.520). The OR for the A/A + A/G genotype, the A/A genotypes, and the A/A vs G/G genotypes in samples overall and in each ethnic group showed a similar trend to those for the TNF-a A allele. Conclusion. This metaanalysis demonstrates that the TNF-a –308 A/G polymorphism may represent a significant risk factor for RA in Latin Americans, but not in Europeans. (First Release Dec 1, 2006; J Rheumatol 2007;34:43–9) Key Indexing Terms:
RHEUMATOID ARTHRITIS From the Division of Rheumatology, Department of Internal Medicine, Korea University Medical Center, College of Medicine, Korea University, Seoul, Korea. Y.H. Lee, MD, PhD, Associate Professor of Rheumatology; J.D. Ji, MD, PhD, Associate Professor of Rheumatology; G.G. Song, MD, PhD, Professor of Rheumatology, Division of Rheumatology, Department of Internal Medicine, Korea University Medical Center, College of Medicine. Address reprint requests to Dr. Y.H. Lee, Division of Rheumatology, Department of Internal Medicine, Korea University Medical Center, 126-1 Ka, Anam-Dong, Seongbuk-Ku, Seoul, 136-705, Korea. E-mail : lyhcgh@korea.ac.kr Accepted for publication September 21, 2006.
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