Abstract
Systemic lupus erythematosus (SLE) is one of the common autoimmune diseases with complex genetic components. To identify a gene(s) susceptible to SLE, we performed a case-control association study using genome-wide gene-based single nucleotide polymorphisms (SNPs) in Japanese population. Here we report that an SNP (rs3748079) located in a promoter region of the inositol 1,4,5-triphosphate receptor type 3 (ITPR3) gene on chromosome 6p21 was significantly associated with SLE in two independent Japanese case-control samples [P = 0.0000000178 with odds ratio of 1.88, 95% confidence interval (CI) of 1.51–2.35]. This particular SNP also revealed associations with rheumatoid arthritis (RA) (P = 0.0084 with odds ratio of 1.23, 95% CI of 1.05–1.43) and with Graves’ disease (GD) (P = 0.00036 with odds ratio of 1.57, 95% CI of 1.22–2.02). We found the binding of NKX2.5 specific to the non-susceptible T allele in the region including this SNP. Furthermore, an SNP in NKX2.5 also revealed an association with SLE (P = 0.0037 with odds ratio of 1.74, 95% CI of 1.19–2.55). Individuals with risk genotype of both ITPR3 and NKX2.5 loci have higher risk for SLE (odds ratio = 5.77). Our data demonstrate that genetic and functional interactions of ITPR3 and NKX2.5 play a crucial role in the pathogenesis of SLE.
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Acknowledgments
We wish to thank Dr. Michiaki Kubo and Dr. Chizu Tanikawa for advice and useful discussion. We are grateful to the members of the Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan for supporting our study.
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Oishi, T., Iida, A., Otsubo, S. et al. A functional SNP in the NKX2.5-binding site of ITPR3 promoter is associated with susceptibility to systemic lupus erythematosus in Japanese population. J Hum Genet 53, 151–162 (2008). https://doi.org/10.1007/s10038-007-0233-3
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DOI: https://doi.org/10.1007/s10038-007-0233-3
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