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MICA and NLRP3 gene polymorphisms interact synergistically affecting the risk of ankylosing spondylitis

Javier Fernández-Torres1,2, Yessica Zamudio-Cuevas3, Xiadani Ruiz-Dávila4

  • 1Laboratorio de Líquido Sinovial, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Calzada México-Xochimilco 289, C.P. 14389, Alcaldía Tlalpan, Mexico City, Mexico. javierastrofan1971@gmail.com.

Immunologic Research
|September 4, 2023
PubMed

Insights

Genetic variants in MICA and NLRP3 genes are associated with ankylosing spondylitis (AS). Specific MICA alleles increase AS risk, while an NLRP3 variant offers protection, with gene interactions identified.

Area of Science:

  • Immunogenetics
  • Rheumatology
  • Molecular Biology

Background:

  • Ankylosing spondylitis (AS) is an autoinflammatory condition impacting the sacroiliac joints, leading to back stiffness and pain.
  • MICA, a ligand for the NKG2D receptor, influences immune responses in various diseases.
  • The role of the NLRP3 inflammasome in AS pathogenesis remains largely unexplored.

Purpose of the Study:

  • To investigate the association and interaction of polymorphic variants in the MICA and NLRP3 genes within a Mexican cohort of AS patients.
  • To identify specific genetic markers contributing to AS susceptibility or protection.

Main Methods:

  • A case-control study design was employed, comparing AS patients with healthy controls of Mexican origin.
  • Genotyping of MICA polymorphisms (rs4349859, rs116488202) and NLRP3 polymorphisms (rs3806268, rs10754558) was performed using TaqMan probes.
  • Statistical analyses included logistic regression for associations and multifactorial dimensionality reduction (MDR) for interaction analysis.

Main Results:

  • The minor alleles of MICA polymorphisms rs4349859 (A) and rs116488202 (T) were significantly associated with an increased risk of AS.
  • The minor allele of the NLRP3 polymorphism rs3806268 (A) demonstrated a protective association against AS.
  • MDR analysis revealed significant synergistic interactions between MICA and NLRP3 polymorphisms, indicating a combined effect on AS risk.

Conclusions:

  • Specific MICA gene variants (rs4349859 A allele, rs116488202 T allele) are risk factors for developing ankylosing spondylitis.
  • An interaction between MICA and NLRP3 genetic variants contributes to the overall genetic susceptibility to AS.
  • These findings highlight the potential role of MICA and NLRP3 in AS pathogenesis and suggest novel therapeutic targets.
Keywords:
Ankylosing spondylitisGene–gene interactionsMICANLRP3Single-nucleotide polymorphisms

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