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.
Kamatani
Yoichiro
Y
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo, 4-6-1 Shirokanedai, Minato, Tokyo, 108-8639, Japan.
Matsuda
Koichi
K
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.
Ohishi
Tetsuya
T
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.
Ohtsubo
Shigeru
S
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.
Yamazaki
Keiko
K
Laboratory for Gastrointestinal Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
Iida
Aritoshi
A
Laboratory for Pharmacogenetics, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
Hosono
Naoya
N
Laboratory for Genotyping, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
Kubo
Michiaki
M
Laboratory for Genotyping, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
Yumura
Wako
W
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Nitta
Kosaku
K
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Katagiri
Toyomasa
T
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo, 4-6-1 Shirokanedai, Minato, Tokyo, 108-8639, Japan.
Kawaguchi
Yasushi
Y
Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
Kamatani
Naoyuki
N
Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
Nakamura
Yusuke
Y
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo, 4-6-1 Shirokanedai, Minato, Tokyo, 108-8639, Japan.
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