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Are SMAD2/4/7 genetic variants associated with rheumatoid arthritis susceptibility and severity?

Anna Wajda1, Barbara Stypińska2, Magdalena Czarnecka2

  • 1Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland. annawajda2046@gmail.com.

Clinical and Experimental Rheumatology
|November 15, 2022
PubMed
Abstract

Insights

Genetic variants in SMAD4 may offer protection against rheumatoid arthritis (RA). Specific SMAD2 and SMAD7 variants are linked to RA disease progression and creatinine levels in Caucasian patients.

Area of Science:

  • Genetics
  • Immunology
  • Rheumatology

Background:

  • SMAD proteins are crucial in TGF-beta signaling, influencing immune responses and fibrosis.
  • Dysregulation of SMADs is implicated in autoimmune connective tissue diseases like rheumatoid arthritis (RA).

Purpose of the Study:

  • To investigate the association of single nucleotide polymorphisms (SNPs) in SMAD2, SMAD4, and SMAD7 with RA risk.
  • To examine the relationship between these SNPs and disease course in RA patients.

Main Methods:

  • Genotyping of 647 RA patients and 496 healthy controls using TaqMan assay.
  • Bioinformatic analysis including TraP-score and PredictSNP.2 for pathogenicity prediction.
  • Association analysis with RA risk, disease course, and creatinine levels.

Main Results:

  • SMAD4 genotypes (rs12456284 AG and rs10502913 GA) were more frequent in healthy individuals, suggesting a protective effect against RA.
  • Strong linkage disequilibrium (LD) observed between rs12456284 and rs10502913 in SMAD4.
  • SMAD2 rs1792666 and SMAD7 rs3736242 showed significant associations with RA disease course; SMAD4 rs10502913, SMAD7 rs3736242, and SMAD7 rs4464148 were linked to creatinine levels.

Conclusions:

  • SMAD4 variants rs12456284 and rs10502913 may confer a protective effect against rheumatoid arthritis in the Caucasian population.
  • SMAD2 rs1792666 and SMAD7 rs3736242 are significantly associated with the disease course of RA.

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