Sui Jiangdong, Li Hua, Fang Yongfei, Liu Yang, Li Minhui, Zhong Bing, Yang Fei, Zou Qiang, Wu Yuzhang
Third Military Medical University College of Basic Medical Sciences, Chongqing, China.
Arthritis Rheum. 2012 Mar;64(3):647-54. doi: 10.1002/art.33370.
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.
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.
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.
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.
炎性小体相关蛋白NLRP1/NALP1与某些自身免疫性疾病的发生和发展有关。本研究旨在确定NLRP1基因多态性是否与中国汉族人群类风湿关节炎（RA）易感性相关，并评估这种关联的功能意义。
对居住在成都的190例RA患者和190例匹配的健康对照进行NLRP1启动子多态性rs6502867和rs878329基因分型。在居住于重庆的另一组1514名受试者中对rs878329进行基因分型。通过双荧光素酶测定评估每种多态性对NLRP1转录的影响，同时通过电泳迁移率变动分析确定对DNA-蛋白质相互作用的影响。通过实时定量聚合酶链反应研究不同基因型个体中NLRP1的差异表达。
多态性rs878329而非rs6502867与RA相关（C等位基因的优势比[OR]为0.83，P = 0.02；CC基因型的OR为0.42，P = 0.01）。rs878329的GG基因型是RA的风险基因型（OR 2.38），并且具有上调NLRP1转录的与 runt相关的转录因子1结合位点。在中国汉族人群中，具有RA风险基因型GG的个体的NLRP1信使RNA水平显著高于具有CC基因型的个体。
我们的研究结果表明NLRP1与中国汉族人群的RA相关。NLRP1启动子中rs878329的G等位基因上调基因转录并赋予RA风险。
