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SLC22A4 Polymorphism and Rheumatoid Arthritis Susceptibility: A Replication Study in a Japanese Population and a Metaanalysis
YUKINORI OKADA, MIKAKO MORI, RYO YAMADA, AKARI SUZUKI, KYOKO KOBAYASHI, MICHIAKI KUBO, YUSUKE NAKAMURA, and KAZUHIKO YAMAMOTO
ABSTRACT. Methods. We conducted a metaanalysis for slc2F1/F2 polymorphisms to RA susceptibility, which included the replication study of an independent Japanese population consisting of 924 cases and 940 controls. A total of 9 studies (4 Japanese studies, 5 Caucasian studies) consisting of 8076 cases and 6837 controls were included in the metaanalysis. Results. The replication study demonstrated significant associations in a Japanese population (OR 1.20, 95% CI 1.04–1.37, p = 0.0099, in the allelic mode; OR 1.29, 95% CI 1.08–1.55, p = 0.006, in the dominant mode; p = 0.011 in the trend mode). Significant ethnic diversities of allele frequencies of slc2F1/F2 polymorphisms were found (p = 8.6*10-8) between Caucasian and Japanese populations (0.07–0.08 and 0.30–0.32, respectively). The metaanalysis demonstrated significant associations for all studies (fixed-effect OR 1.11, 95% CI 1.05–1.18, p = 0.00084; random-effect OR 1.10, 95% CI 1.02–1.19, p = 0.017 in the allelic mode). Although subgroup analysis did not detect a significant association within Caucasian studies, significant associations were found within Japanese studies (fixed-effect and random-effect OR 1.16, 95% CI 1.07–1.25, p = 0.00012 in the allelic mode). Conclusion. The associations in Caucasian studies were not significant. Since the significantly low frequency of the risk allele made statistical power lower in Caucasians than in Japanese, whether significant relative risks existed in Caucasian populations was inconclusive. The significant relative risks in Japanese populations were confirmed. (First Release Aug 15 2008; J Rheumatol 2008;35:1723–8) Key Indexing Terms:
RHEUMATOID ARTHRITIS
From the Laboratory of Functional Genomics, Human Genome Center, Institute of Medical Science, the University of Tokyo, Tokyo; Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo; the Laboratory for Rheumatic Diseases, and the Laboratory for Genotyping, SNP Research Center, Institute of Physical and Chemical Research (RIKEN), Yokohama; and the Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo, Tokyo, Japan. Supported by a grant from the Japanese Millennium Project, a grant from SNP Research Center, RIKEN, a grant for Research on Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan, and a grant for Research on Human Genome Tailor-Made from the Ministry of Health, Labour and Welfare of Japan. Y. Okada, MD; R. Yamada, MD, PhD, Laboratory of Functional Genomics, Human Genome Center, Institute of Medical Science, the University of Tokyo; M. Mori, MD, PhD; K. Yamamoto, MD, PhD, Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo and Laboratory for Rheumatic Diseases, SNP Research Center, Institute of Physical and Chemical Research (RIKEN); A. Suzuki, PhD; K. Kobayashi, BS, Laboratory for Rheumatic Diseases, SNP Research Center, Institute of Physical and Chemical Research (RIKEN); M. Kubo, MD, PhD, Laboratory for Genotyping, SNP Research Center, Institute of Physical and Chemical Research (RIKEN); Y. Nakamura, MD, PhD, Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo. Address reprint requests to Dr. R. Yamada, Laboratory of Functional Genomics, Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. E-mail: ryamada@src.riken.go.jp Accepted for publication April 22, 2008. |
