論文 - 詳細
| RRC ID | 68500 |
|---|---|
| 著者 | Tokuhiro S, Yamada R, Chang X, Suzuki A, Kochi Y, Sawada T, Suzuki M, Nagasaki M, Ohtsuki M, Ono M, Furukawa H, Nagashima M, Yoshino S, Mabuchi A, Sekine A, Saito S, Takahashi A, Tsunoda T, Nakamura Y, Yamamoto K. |
| タイトル | An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis. |
| ジャーナル | Nat Genet |
| Abstract |
Rheumatoid arthritis is a common inflammatory disease with complex genetic components. We investigated the genetic contribution of the cytokine gene cluster in chromosome 5q31 to susceptibility to rheumatoid arthritis in the Japanese population by case-control linkage disequilibrium (LD) mapping using single nucleotide polymorphisms (SNPs). Here we report that there is significant association between rheumatoid arthritis and the organic cation transporter gene SLC22A4 (P = 0.000034). We show that expression of SLC22A4 is specific to hematological and immunological tissues and that SLC22A4 is also highly expressed in the inflammatory joints of mice with collagen-induced arthritis. A SNP affects the transcriptional efficiency of SLC22A4 in vitro, owing to an allelic difference in affinity to Runt-related transcription factor 1 (RUNX1), a transcriptional regulator in the hematopoietic system. A SNP in RUNX1 is also strongly associated with rheumatoid arthritis (P = 0.00035). Our data indicate that the regulation of SLC22A4 expression by RUNX1 is associated with susceptibility to rheumatoid arthritis, which may represent an example of an epistatic effect of two genes on this disorder. |
| 巻・号 | 35(4) |
| ページ | 341-8 |
| 公開日 | 2003-12-1 |
| DOI | 10.1038/ng1267 |
| PII | ng1267 |
| PMID | 14608356 |
| MeSH | Animals Arthritis, Rheumatoid / chemically induced Arthritis, Rheumatoid / genetics* Carrier Proteins / genetics Case-Control Studies Chromosomes, Human, Pair 5 / genetics Collagen / pharmacology Core Binding Factor Alpha 2 Subunit Cytokines / genetics DNA-Binding Proteins / genetics* Electrophoretic Mobility Shift Assay Female Gene Frequency Genetic Predisposition to Disease Humans Introns / genetics* Jurkat Cells Linkage Disequilibrium* Luciferases Male Membrane Proteins / genetics Mice Middle Aged Organic Anion Transporters / genetics* Organic Cation Transport Proteins* Polymorphism, Single Nucleotide / genetics* Promoter Regions, Genetic Proto-Oncogene Proteins* Solute Carrier Family 22 Member 5 Transcription Factors / genetics* |
| IF | 27.605 |
| リソース情報 | |
| ヒト・動物細胞 | THP-1(RCB1189) |