Association of HLA-B alleles with familial mediterranean fever (FMF): A comparative study
Utku Aksu1, Pınar Aksu Kılıçle2, Sevim Gönen3
1Gazi University Faculty of Medicine, Ankara, Türkiye.
Objective:
Familial Mediterranean Fever (FMF) is the most prevalent monogenic autoinflammatory disorder. In the present study, we investigated whether HLA-B polymorphisms contribute to familial Mediterranean fever (FMF) susceptibility and phenotypic variability.
Methods:
We enrolled 50 familial Mediterranean fever (FMF) patients, 40 asymptomatic Mediterranean FeVer (MEFV) mutation carriers, and 50 healthy controls. HLA-B genotypes were determined by the PCR-SSO technique. Allele frequencies were compared using chi-square or Fisher's exact tests.
Results:
HLA-B*51 and HLA-B*35 alleles were enriched among FMF patients compared with controls (p = 0.01 and p = 0.03, respectively). HLA-B*27 was moderately increased in patients (p = 0.04), while HLA-B*44 tended to be more common in carriers (p = 0.07). Odds ratio (OR) and confidence interval (CI) analyses indicated an elevated FMF risk for carriers of HLA-B*51 and HLA-B*35.
Conclusion:
HLA-B variants, particularly B*51 and B*35, may act as immunogenetic modifiers of FMF, supporting the concept of MHC class I linked inflammatory pathways contributing to disease heterogeneity.
Insights
Certain HLA-B gene variations, specifically HLA-B*51 and HLA-B*35, are linked to an increased risk and varied severity of Familial Mediterranean Fever (FMF). This suggests a role for these immune system genes in FMF development.
Area of Science:
- Immunogenetics
- Autoinflammatory Diseases
- Human Genetics
Background:
- Familial Mediterranean Fever (FMF) is a common monogenic autoinflammatory condition.
- The genetic underpinnings of FMF susceptibility and its diverse clinical presentations require further elucidation.
Purpose of the Study:
- To investigate the association between Human Leukocyte Antigen (HLA)-B polymorphisms and FMF.
- To determine if specific HLA-B alleles influence FMF susceptibility and phenotypic variability.
Main Methods:
- Genotyping of HLA-B alleles in 50 FMF patients, 40 asymptomatic MEFV mutation carriers, and 50 healthy controls using PCR-SSO.
- Statistical comparison of allele frequencies between groups using chi-square or Fisher's exact tests.
Main Results:
- Enrichment of HLA-B*51 and HLA-B*35 alleles in FMF patients compared to controls (p<0.05).
- Moderate increase of HLA-B*27 in patients; HLA-B*44 showed a trend in carriers.
- HLA-B*51 and HLA-B*35 confer an elevated risk for FMF.
Conclusions:
- HLA-B variants, particularly B*51 and B*35, may modify FMF susceptibility and clinical outcomes.
- These findings support the involvement of MHC class I-related inflammatory pathways in FMF pathogenesis and heterogeneity.
