Association ofTNFAIP3Polymorphism with Susceptibility to Systemic Lupus Erythematosus in a Japanese Population

Aya Kawasaki,Yoshinari Takasaki,Daisuke Goto,Ikue Ito,Satoshi Ito,Hiroshi Hashimoto,Naoyuki Tsuchiya,Taichi Hayashi,Takayuki Sumida,Isao Matsumoto

doi:10.1155/2010/207578

Abstract

Recent genome-wide association studies demonstrated association of single nucleotide polymorphisms (SNPs) in the TNFAIP3 region at 6q23 with systemic lupus erythematosus (SLE) in European-American populations. In this study, we investigated whether SNPs in the TNFAIP3 region are associated with SLE also in a Japanese population. A case-control association study was performed on the SNPs rs13192841, rs2230926, and rs6922466 in 318 Japanese SLE patients and 444 healthy controls. Association of rs2230926 G allele with SLE was replicated in Japanese (allelic association P = .033, odds ratio [OR] 1.47, recessive model P = .023, OR 8.52). The association was preferentially observed in the SLE patients with nephritis. When the TNFAIP3 mRNA levels of the HapMap samples were examined using GENEVAR database, the presence of TNFAIP3 rs2230926 G allele was associated with lower mRNA expression of TNFAIP3 (P = .013). These results indicated that TNFAIP3 is a susceptibility gene to SLE both in the Caucasian and Asian populations.

Highlights

Nuclear factor-κB (NF-κB) is a transcription factor that regulates expression of various genes including pro-inflammatory cytokines
Association of TNFAIP3 rs2230926 genotype with TNFAIP3 mRNA expression was examined using the mRNA data from lymphoblastoid cell lines derived from JPT and CHB HapMap individuals available from the database of the Gene Expression Variation (GENEVAR) project at the Wellcome Trust Sanger Institute, as previously described [11]
To examine whether TNFAIP3 is associated with systemic lupus erythematosus (SLE) in a Japanese population, an association study of rs13192841, rs2230926, and rs6922466 was conducted in 318 Japanese patients with SLE and 444 healthy controls

Summary

Introduction

Nuclear factor-κB (NF-κB) is a transcription factor that regulates expression of various genes including pro-inflammatory cytokines. We carried out a case-control association study of the SNPs in the TNFAIP3 region to examine whether TNFAIP3 is involved in genetic predisposition to SLE in Japanese. A case-control association study was conducted in 318 Japanese patients with SLE (19 males and 299 females, mean ± SD age 41.4 ± 13.5 years) and 444 healthy controls (219 males and 225 females, mean ± SD age 34.0 ± 9.9 years), recruited at the University of Tsukuba, Juntendo University, and the University of Tokyo.

Results

Conclusion