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MEFV variants as phenotypic modifiers in ankylosing spondylitis: a genetic interaction analysis with HLA-B27

Zeynep Irmak Kaya1, Timuçin Kaşifoğlu2

  • 1Department of Internal Medicine Eskişehir, Eskişehir City Hospital, Health Science University, Eskişehir, Türkiye.

Acta Clinica Belgica
|June 19, 2026
PubMed
Abstract

Insights

MEFV variants do not increase ankylosing spondylitis (AS) risk but worsen structural damage in HLA-B27 positive patients. This genetic interaction identifies a high-risk subgroup for targeted monitoring.

Area of Science:

  • Genetics
  • Rheumatology
  • Immunology

Background:

  • Prevalence of MEFV mutations in Mediterranean populations.
  • Unclear role of MEFV variants in ankylosing spondylitis (AS) pathogenesis.
  • Investigating MEFV variants' interaction with HLA-B27 in AS.

Purpose of the Study:

  • Determine if MEFV variants influence AS susceptibility.
  • Assess the impact of MEFV variants on AS disease phenotype.
  • Examine the interaction between MEFV variants and HLA-B27 in AS.

Main Methods:

  • Cross-sectional study of 129 AS patients, 51 RA controls, and 58 healthy controls.
  • Genotyping for 11 MEFV mutations using pyrosequencing.
  • Radiographic severity assessed by BASRI; multivariate regression with interaction term (HLA-B27×MEFV).

Main Results:

  • MEFV carrier frequencies were similar across AS, RA, and control groups (p=0.582).
  • Disease duration and male sex predicted BASRI scores, but not HLA-B27 or MEFV alone.
  • Significant HLA-B27×MEFV interaction (p=0.012) associated with higher BASRI scores in double-positive individuals.

Conclusions:

  • MEFV variants do not confer primary susceptibility to AS.
  • MEFV variants are associated with increased structural involvement in HLA-B27-positive AS patients.
  • Identifies a high-risk genetic subgroup in endemic populations for early intervention.
Keywords:
HLA-B27 antigenMEFV mutationankylosing spondylitisgene–gene interaction

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