An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis
Autor: | Akari Suzuki, Shinichi Yoshino, Akihiro Sekine, Xiaotian Chang, Yuta Kochi, Akihiko Mabuchi, Hidehiko Furukawa, Masakatsu Suzuki, Tatsuhiko Tsunoda, Tetsuji Sawada, Yusuke Nakamura, Susumu Saito, Shinya Tokuhiro, Kazuhiko Yamamoto, Masakazu Nagashima, Masahiko Ohtsuki, Miyuki Nagasaki, Mitsuru Ono, Atsushi Takahashi, Ryo Yamada |
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Rok vydání: | 2003 |
Předmět: |
Male
Linkage disequilibrium Organic Cation Transport Proteins Organic Anion Transporters Arthritis Electrophoretic Mobility Shift Assay Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Linkage Disequilibrium Arthritis Rheumatoid Jurkat Cells Mice Gene Frequency Proto-Oncogene Proteins Genetics medicine Transcriptional regulation Animals Humans SNP Genetic Predisposition to Disease Luciferases Promoter Regions Genetic Solute Carrier Family 22 Member 5 Gene Membrane Proteins Middle Aged medicine.disease Introns DNA-Binding Proteins Case-Control Studies Rheumatoid arthritis Core Binding Factor Alpha 2 Subunit Intronic SNP Chromosomes Human Pair 5 Cytokines Female Collagen Carrier Proteins Transcription Factors |
Zdroj: | Nature Genetics. 35:341-348 |
ISSN: | 1546-1718 1061-4036 |
Popis: | 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. |
Databáze: | OpenAIRE |
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