論文 - 詳細
RRC ID | 43582 |
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著者 | Sui J, Li H, Fang Y, Liu Y, Li M, Zhong B, Yang F, Zou Q, Wu Y. |
タイトル | NLRP1 gene polymorphism influences gene transcription and is a risk factor for rheumatoid arthritis in han chinese. |
ジャーナル | Arthritis Rheum |
Abstract |
OBJECTIVE:The inflammasome-related protein NLRP1/NALP1 has been implicated in the onset and progression of some autoimmune diseases. This study was undertaken to determine whether a polymorphism in the NLRP1 gene is associated with susceptibility to rheumatoid arthritis (RA) in Han Chinese and to assess the functional implications of this association. METHODS:RA patients (n = 190) and matched healthy controls (n = 190) residing in the city of Chengdu were genotyped for the NLRP1 promoter polymorphisms rs6502867 and rs878329. Genotyping for rs878329 was performed in a second set of subjects (n = 1,514) residing in the city of Chongqing. The effect of each polymorphism on NLRP1 transcription was evaluated by dual-luciferase assay, while the effect on DNA protein interaction was determined by electrophoretic mobility shift assay. Differential expression of NLRP1 in individuals with different genotypes was investigated by real-time quantitative polymerase chain reaction. RESULTS:The polymorphism rs878329, but not rs6502867, was associated with RA (odds ratio [OR] 0.83, P = 0.02 for the C allele; OR 0.42, P = 0.01 for the CC genotype). The GG genotype of rs878329 was the risk genotype for RA (OR 2.38) and had a runt-related transcription factor 1 binding site that up-regulated NLRP1 transcription. Individuals with the RA risk genotype GG had significantly higher NLRP1 messenger RNA levels than those with the CC genotype among the Han Chinese population. CONCLUSION:Our findings indicate that NLRP1 is associated with RA in Han Chinese. The G allele of rs878329 in the NLRP1 promoter up-regulates gene transcription and confers the risk of RA. |
巻・号 | 64(3) |
ページ | 647-54 |
公開日 | 2012-3-1 |
DOI | 10.1002/art.33370 |
PMID | 21976003 |
MeSH | Adaptor Proteins, Signal Transducing / genetics* Apoptosis Regulatory Proteins / genetics* Arthritis, Rheumatoid / ethnology Arthritis, Rheumatoid / genetics* Asian People / genetics* China / epidemiology Female Genetic Predisposition to Disease* Genotype HeLa Cells Humans Linkage Disequilibrium Male NLR Proteins Polymorphism, Single Nucleotide* Transcription, Genetic Up-Regulation |
引用数 | 54 |
WOS 分野 | RHEUMATOLOGY |
リソース情報 | |
ヒト・動物細胞 | HeLa(RCB0007) |