Association of IRF5 polymorphisms with systemic lupus erythematosus in a Japanese population: support for a crucial role of intron 1 polymorphisms
| Autor: | Yoshinari Takasaki, Hiroshi Hashimoto, Katsushi Tokunaga, Chieko Kyogoku, Makio Kusaoi, Aya Kawasaki, Timothy W. Behrens, Risa Miyashita, Naoyuki Tsuchiya, Koki Hikami, Jun Ohashi |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Linkage disequilibrium Genotype Immunology Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide White People Exon Rheumatology Asian People Gene Frequency Japan medicine Immunology and Allergy SNP Humans Lupus Erythematosus Systemic Pharmacology (medical) Genetic Predisposition to Disease RNA Messenger Allele frequency Genetics Lupus erythematosus Haplotype Middle Aged medicine.disease Introns Haplotypes Case-Control Studies Interferon Regulatory Factors Female IRF5 |
| Zdroj: | Arthritis and rheumatism. 58(3) |
| ISSN: | 0004-3591 |
| Popis: | Objective To determine whether the IRF5 gene, which encodes interferon regulatory factor 5, is associated with systemic lupus erythematosus (SLE) in a Japanese population. Methods A case–control study was performed in 277 SLE patients and 201 healthy controls. Associations between the IRF5 genotype and levels of messenger RNA (mRNA) for interferon (IFN) pathway genes were examined using an mRNA expression database of HapMap samples. Results Carriers of the rs2004640T single-nucleotide polymorphism (SNP) were slightly increased among SLE patients (58.8%) as compared with controls (50.2%). When data from our Japanese population were combined with previously published data from a Korean population, the T allele frequency was found to be significantly increased in SLE patients (P = 8.3 × 10−5). While no association was observed for the rs10954213 SNP or the exon 6 insertion/deletion, significant associations with 3 intron 1 SNPs (−4001, rs6953165, and rs41298401) were found. The allele frequency of rs41298401G was significantly decreased in SLE patients (13.0% versus 18.7% in controls; P = 0.017), and the allele frequency of rs6953165G, which was in absolute linkage disequilibrium with −4001A, was increased in SLE patients (8.8% versus 5.2% in controls; P = 0.034). The Caucasian risk haplotype was not present; instead, a protective haplotype carrying rs2004640G, rs41298401G, the deletion in exon 6, and rs10954213A was identified. SNP rs10954213, but not intron 1 SNPs, was associated with IRF5 at the mRNA level; nevertheless, intron 1 SNPs were also associated with levels of mRNA for several IFN pathway genes, suggesting a functional role. Conclusion IRF5 was found to be associated with SLE in Asian populations. Intron 1 SNPs, rather than exon 6 and 3′-untranslated region polymorphisms, appeared to play a crucial role. |
| Databáze: | OpenAIRE |
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