NLRP1 gene polymorphism influences gene transcription and is a risk factor for rheumatoid arthritis in han chinese

Arthritis Rheum. 2012 Mar;64(3):647-54. doi: 10.1002/art.33370.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Apoptosis Regulatory Proteins / genetics*
  • Arthritis, Rheumatoid / ethnology
  • Arthritis, Rheumatoid / genetics*
  • Asians / genetics*
  • China / epidemiology
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • HeLa Cells
  • Humans
  • Linkage Disequilibrium
  • Male
  • NLR Proteins
  • Polymorphism, Single Nucleotide*
  • Transcription, Genetic
  • Up-Regulation


  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • NLR Proteins
  • NLRP1 protein, human