Identification of a significant association of a single nucleotide polymorphism in TNXB with systemic lupus erythematosus in a Japanese population.
Systemic lupus erythematosus (SLE) is one of the common autoimmune diseases, with complex genetic components. Here, we report on a case-control association study of 178 SLE patients and 899 control subjects, using genome-wide gene-based single nucleotide polymorphism (SNP) markers. An SNP, rs3130342, in a 5' flanking region of the TNXB gene revealed a significant association with SLE [P = 0.000000930, odds ratio (OR) 3.11, with 95% confidence interval (95%CI) of 1.89-5.28] in a Japanese population. This association was replicated independently with 203 cases and 294 controls (P = 0.0440, OR 1.52, with 95%CI of 1.01-2.78). Although a copy number variation (CNV) of the C4 gene adjacent to the TNXB gene was reported to be associated with SLE, our analysis on this CNV revealed that the association of CNV of the C4 gene was weaker than the SNP in the TNXB gene and likely to reflect the linkage disequilibrium between C4 CNV and this particular SNP. Stratified analysis also revealed that the association of SNP rs3130342 with SLE was independent of the HLA-DRB1*1501 allele that has been shown to be associated with SLE. Our findings strongly imply that the TNXB gene is a candidate gene susceptible to SLE in the Japanese population.
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo, 4-6-1 Shirokanedai, Minato, Tokyo, 108-8639, Japan.
Yoichiro
Y
Kamatani
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo, 4-6-1 Shirokanedai, Minato, Tokyo, 108-8639, Japan. koichima@ims.u-tokyo.ac.jp.
Koichi
K
Matsuda
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo, 4-6-1 Shirokanedai, Minato, Tokyo, 108-8639, Japan.|Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Tetsuya
T
Ohishi
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo, 4-6-1 Shirokanedai, Minato, Tokyo, 108-8639, Japan.|Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Shigeru
S
Ohtsubo
Laboratory for Gastrointestinal Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
Keiko
K
Yamazaki
Laboratory for Pharmacogenetics, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
Aritoshi
A
Iida
Laboratory for Genotyping, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
Naoya
N
Hosono
Laboratory for Genotyping, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
Michiaki
M
Kubo
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Wako
W
Yumura
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Kosaku
K
Nitta
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo, 4-6-1 Shirokanedai, Minato, Tokyo, 108-8639, Japan.
Toyomasa
T
Katagiri
Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
Yasushi
Y
Kawaguchi
Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
Naoyuki
N
Kamatani
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo, 4-6-1 Shirokanedai, Minato, Tokyo, 108-8639, Japan.
Yusuke
Y
Nakamura
D002896:Chromosomes, Human, Pair 6; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019063:Tenascin / Q000235:genetics*
D019063:Tenascin; C081865:tenascin X