Linked Life Data

18219441

Source:http://linkedlifedata.com/resource/pubmed/id/18219441

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pubmed-article:18219441pubmed:abstractTextSystemic 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.lld:pubmed
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pubmed-article:18219441pubmed:articleTitleA functional SNP in the NKX2.5-binding site of ITPR3 promoter is associated with susceptibility to systemic lupus erythematosus in Japanese population.lld:pubmed
pubmed-article:18219441pubmed:affiliationLaboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo, 4-6-1 Shirokanedai, Minato, Tokyo, 108-8639, Japan.lld:pubmed
pubmed-article:18219441pubmed:publicationTypeJournal Articlelld:pubmed
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