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Association of TNFAIP3 interacting protein 1, TNIP1 with systemic lupus erythematosus in a Japanese population: a case-control association study |
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| Authors: | Aya Kawasaki Satoshi Ito Hiroshi Furukawa Taichi Hayashi Daisuke Goto Isao Matsumoto Makio Kusaoi Jun Ohashi Robert R Graham Kunio Matsuta Timothy W Behrens Shigeto Tohma Yoshinari Takasaki Hiroshi Hashimoto Takayuki Sumida Naoyuki Tsuchiya |
| Institution: | 1. Molecular and Genetic Epidemiology Laboratory, Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan 2. Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan 3. Department of Rheumatology, Niigata Rheumatic Center, 1-2-8 Hon-cho, Shibata, Niigata, 957-0054, Japan 4. Department of Rheumatology, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, National Hospital Organization, 18-1 Sakuradai, Minami-ku, Sagamihara, Kanagawa, 252-0392, Japan 5. Division of Rheumatology, Department of Internal Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan 6. Immunology Biomarkers Group, Genentech, Inc. 1 DNA Way, South San Francisco, California, 94080-4990, USA 7. Matsuta Clinic, 2-28-8 Daizawa, Setagaya-ku, Tokyo, 115-0032, Japan 8. Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan |
| Abstract: | IntroductionTNFAIP3 interacting protein 1, TNIP1 (ABIN-1) is involved in inhibition of nuclear factor-κB (NF-κB) activation by interacting with TNF alpha-induced protein 3, A20 (TNFAIP3), an established susceptibility gene to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Recent genome-wide association studies revealed association of TNIP1 with SLE in the Caucasian and Chinese populations. In this study, we investigated whether the association of TNIP1 with SLE was replicated in a Japanese population. In addition, association of TNIP1 with RA was also examined.MethodsA case-control association study was conducted on the TNIP1 single nucleotide polymorphism (SNP) rs7708392 in 364 Japanese SLE patients, 553 RA patients and 513 healthy controls.ResultsAssociation of TNIP1 rs7708392C was replicated in Japanese SLE (allele frequency in SLE: 76.5%, control: 69.9%, P = 0.0022, odds ratio OR] 1.40, 95% confidence interval CI] 1.13-1.74). Notably, the risk allele frequency in the healthy controls was considerably greater in Japanese (69.9%) than in Caucasians (24.3%). A tendency of stronger association was observed in the SLE patients with renal disorder (P = 0.00065, OR 1.60 95%CI 1.22-2.10]) than in all SLE patients (P = 0.0022, OR 1.40 95%CI 1.13-1.74]). Significant association with RA was not observed, regardless of the carriage of human leukocyte antigen DR β1 (HLA-DRB1) shared epitope. Significant gene-gene interaction between TNIP1 and TNFAIP3 was detected neither in SLE nor RA.ConclusionsAssociation of TNIP1 with SLE was confirmed in a Japanese population. TNIP1 is a shared SLE susceptibility gene in the Caucasian and Asian populations, but the genetic contribution appeared to be greater in the Japanese and Chinese populations because of the higher risk allele frequency. Taken together with the association of TNFAIP3, these observations underscore the crucial role of NF-κB regulation in the pathogenesis of SLE. |
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