論文 - 詳細
| RRC ID | 43246 |
|---|---|
| 著者 | Oishi T, Iida A, Otsubo S, Kamatani Y, Usami M, Takei T, Uchida K, Tsuchiya K, Saito S, Ohnisi Y, Tokunaga K, Nitta K, Kawaguchi Y, Kamatani N, Kochi Y, Shimane K, Yamamoto K, Nakamura Y, Yumura W, Matsuda K. |
| タイトル | A functional SNP in the NKX2.5-binding site of ITPR3 promoter is associated with susceptibility to systemic lupus erythematosus in Japanese population. |
| ジャーナル | J Hum Genet |
| 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. |
| 巻・号 | 53(2) |
| ページ | 151-162 |
| 公開日 | 2008-1-1 |
| DOI | 10.1007/s10038-007-0233-3 |
| PII | 10.1007/s10038-007-0233-3 |
| PMID | 18219441 |
| MeSH | Adult Arthritis, Rheumatoid / genetics Binding Sites Case-Control Studies Chromatin Immunoprecipitation Cohort Studies Female Genetic Predisposition to Disease* Genotype Graves Disease / genetics Homeobox Protein Nkx-2.5 Homeodomain Proteins / genetics Homeodomain Proteins / metabolism* Humans Inositol 1,4,5-Trisphosphate Receptors / genetics* Japan / epidemiology Luciferases / metabolism Lupus Erythematosus, Systemic / genetics* Middle Aged Polymorphism, Single Nucleotide / genetics* Promoter Regions, Genetic / genetics* RNA, Messenger / genetics RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Transcription Factors / genetics Transcription Factors / metabolism* |
| IF | 2.831 |
| 引用数 | 19 |
| WOS 分野 | GENETICS & HEREDITY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) |