NLRP1 gene polymorphism influences gene transcription and is a risk factor for rheumatoid arthritis in Han Chinese

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.