Association of tyrosine kinase 2 polymorphisms with susceptibility to microscopic polyangiitis in a Guangxi population

PeerJ. 2024 Dec 23:12:e18735. doi: 10.7717/peerj.18735. eCollection 2024.

Abstract

Background: Heredity and epigenetics affect the pathogenesis of microscopic polyangiitis (MPA). Tyrosine kinase 2 (TYK2) polymorphisms (rs2304256C > A, rs280519A > G, and rs12720270G > A) may be potential protective factors against anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Current research suggests that TYK2 is associated with various autoimmune diseases; however, no study has examined the relationship between TYK2 polymorphisms and AAV. This study assessed the effect of TYK2 polymorphisms on susceptibility to MPA.

Methods: Overall, 562 Chinese participants (265 patients with MPA and 297 healthy volunteers) were recruited. Polymerase chain reactions combined with high-throughput sequencing were used to analyze polymorphic loci, while logistic regression analysis was used to assess the relationship between polymorphism of the TYK2 gene and MPA susceptibility.

Results: In males, individuals with the CA genotype (rs2304256) in the overdominant model showed a significantly reduced risk of MPA (odds ratio (OR) = 0.52; 95% confidence interval (CI) [0.29-0.93]; p = 0.025). Regarding rs280519, male carriers of the AG genotype had a significantly lower risk of developing MPA in both the codominant (OR = 0.51; 95% CI [0.28-0.93]; p = 0.039) and overdominant (OR = 0.48; 95% CI [0.27-0.86]; p = 0.013) models. The GA genotype of rs12720270 was associated with low susceptibility to MPA in males (OR = 0.52; 95% CI [0.29-0.93]; p = 0.027).

Conclusions: This study indicates that mutations in the TYK2 gene (rs2304256, rs280519, and rs12720270) may be associated with a reduced risk of MPA in the male Chinese population in Guangxi. The A allele of single nucleotide polymorphism (SNP) rs2304256 may be a protective factor against MPA, while the G alleles of SNPs rs280519 and rs12720270 are protective factors against MPA.

Keywords: Microscopic polyangiitis; Polymorphism; Susceptibility; TYK2.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • China / epidemiology
  • East Asian People / genetics
  • Female
  • Genetic Predisposition to Disease* / genetics
  • Genotype
  • Humans
  • Male
  • Microscopic Polyangiitis* / epidemiology
  • Microscopic Polyangiitis* / genetics
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • TYK2 Kinase* / genetics

Substances

  • TYK2 Kinase
  • TYK2 protein, human

Grants and funding

This work was supported by Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation under Grant (2024GXNSFAA999092), the Guangxi Health Commission Key Laboratory of Medical Genetics and Genomic (GXKMGG202303), Guangxi Natural Science Foundation Program (No. 2018GXNSFAA281122), the Guangxi Health Commission self-financial project (No. Z-A20230648). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.