Association of STAT4, TGFβ1, SH2B3 and PTPN22 polymorphisms with autoimmune hepatitis

Exp Mol Pathol. 2018 Dec;105(3):279-284. doi: 10.1016/j.yexmp.2018.10.001. Epub 2018 Oct 3.

Abstract

The physiopathology of autoimmune hepatitis (AIH) is complex and still not fully elucidated. The genes localized outside the histocompatibility complex involved in regulation and signal transduction of the immune system SH2B3, TGFβ1, STAT4 and PTPN22 could be associated to the susceptibility and hepatocyte lysis mechanism of this lethal autoimmune disorder.

Patients and methods: We investigated four polymorphic sites in SH2B3 (rs3184504), TGFβ1 (rs1800471), STAT4 (rs7574865) and PTPN22 (rs2476601) in 45 AIH patients and 150 healthy controls from Tunisia using real-time PCR.

Results: Significant associations were found for SH2B3 T allele (OR = 1.861; p = 0.015, pc = 0.366) and PTPN22 A allele (OR = 7.070; p = 0.026; pc = 1.00) and AIH with opposite homozygous being protective against the disease (CC genotype with OR = 0.420, p = 0.025; GG genotype with OR = 0.136, p = 0.025, respectively). No statistically significant associations were found for the TGFβ1 and STAT4 polymorphisms with AIH susceptibility.

Conclusion: Our work enlarges information on non-HLA genes that are associated with AIH by focusing in a region of the world that was poorly molecularly characterized for this disease.

Keywords: And PTPN22; Autoimmune hepatitis; Genetic susceptibility; SH2B3; STAT4; TGFβ1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Hepatitis, Autoimmune / genetics*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics*
  • Proteins / genetics*
  • STAT4 Transcription Factor / genetics
  • Transforming Growth Factor beta1 / genetics
  • Tunisia

Substances

  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • SH2B3 protein, human
  • STAT4 Transcription Factor
  • STAT4 protein, human
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22