The association of NLRP3 and TNFRSF1A polymorphisms with risk of ankylosing spondylitis and treatment efficacy of etanercept

J Clin Lab Anal. 2017 Nov;31(6):e22138. doi: 10.1002/jcla.22138. Epub 2017 Jan 23.

Abstract

Background: To discover how NLRP3 and TNFRSF1A polymorphisms affect the efficacy of traditional medicine and etanercept for ankylosing spondylitis (AS) patients.

Methods: Single nucleotide polymorphism (SNP) and haplotype analyses were conducted based on determined NLRP3 and TNFRSF1A among AS patients. We subsequently analyzed the relationship between relevant clinical indexes and polymorphisms of NLRP3 and TNFRSF1A.

Results: The 4 SNP loci on NLRP3 and 3 SNP loci on TNFRSF1A showed significant linkage disequilibrium, respectively. The T allele of NLRP3 rs4612666 and the T allele of TFRSF1A rs4149570 are both associated with AS (P<.05). The T-A-C-T haplotype of NLRP3 as well as the G-C-C, T-C-C, T-C-T, and T-T-T haplotypes of TFRSF1A are associated with AS (P<.05). The morning stiffness time, BASDAI scoring, and ESR of patients receiving etanercept were significantly higher than those receiving traditional medicine. T allele of NLRP3 rs4612666 had a significantly greater negative impact on the ASAS20 improvement than C allele. Whereas the A allele of NLRP3 rs3806268 had a significantly greater positive impact on the ASAS20 improvement than G allele. There is no significant association between SNP and efficacy of traditional medicine in the treatment of AS.

Conclusion: NLRP3 and TFRSF1A (rs4149570) are associated with AS susceptibility. There is a significant association between NLRP3 polymorphisms and treatment of etanercept.

Keywords: NLRP3; TNFRSF1A; ankylosing spondylitis; etanercept; single nucleotide polymorphism.

MeSH terms

  • Adolescent
  • Adult
  • Cohort Studies
  • Etanercept / therapeutic use*
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Tumor Necrosis Factor, Type I / genetics*
  • Spondylitis, Ankylosing* / drug therapy
  • Spondylitis, Ankylosing* / epidemiology
  • Spondylitis, Ankylosing* / genetics
  • Young Adult

Substances

  • Immunosuppressive Agents
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Receptors, Tumor Necrosis Factor, Type I
  • TNFRSF1A protein, human
  • Etanercept