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Variants within STAT genes reveal association with anticitrullinated protein antibody-negative rheumatoid arthritis

Maria Seddighzadeh1, Antonio Gonzalez, Bo Ding

  • 1Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. maria.seddighzadeh@ki.se

The Journal of Rheumatology
|July 4, 2012
PubMed

Insights

Genetic variations in STAT genes are linked to rheumatoid arthritis (RA) susceptibility. Specific STAT polymorphisms are associated with anticitrullinated protein antibody-negative RA, suggesting differential roles in disease subtypes.

Area of Science:

  • Immunogenetics
  • Rheumatology

Background:

  • Signal transducer and activator of transcription (STAT) proteins, including STAT3 and STAT4, are crucial for immune responses like the T helper 1 (Th1) response mediated by interleukin-12 (IL-12) and the survival of Th17 cells.
  • Rheumatoid arthritis (RA) is a complex autoimmune disease with distinct serological subgroups, such as those defined by the presence or absence of anticitrullinated protein antibodies (ACPA).

Purpose of the Study:

  • To investigate the association between single-nucleotide polymorphisms (SNP) in STAT3 and STAT4 genes and serologically distinct subgroups of rheumatoid arthritis (RA).

Main Methods:

  • A comprehensive analysis of 41 SNP within the STAT1-STAT4 loci was conducted in a Swedish cohort comprising 2043 RA cases and 1115 controls.
  • Nine promising SNP were further validated in an independent Spanish cohort (1223 RA cases, 1090 controls).

Main Results:

  • Fourteen SNP in STAT3 and STAT1-STAT4 loci showed significant association with ACPA-negative RA in the Swedish cohort.
  • Following validation in the Spanish cohort, three STAT4 SNP and two STAT3 SNP remained associated with ACPA-negative RA.
  • Two STAT4 SNP (rs7574865 and rs10181656) were associated with ACPA-positive RA in the Swedish cohort, with rs7574865 showing consistent association across multiple studies in a meta-analysis.

Conclusions:

  • Genetic variants within STAT genes appear to play a differential role in the susceptibility to rheumatoid arthritis, distinguishing between ACPA-positive and ACPA-negative disease phenotypes.
  • These findings highlight the potential of STAT gene polymorphisms as biomarkers for specific RA subgroups.
Abstract

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