Abstract
Objectives. We aimed to investigate whether five potential functional haplotypes of the glucocorticoid receptor (GR) gene and a single-nucleotide polymorphism of 11 beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) are associated with clinical outcome in ANCA-associated vasculitis.
Methods. Patients diagnosed with ANCA-associated vasculitis (n=241) were genotyped for five polymorphisms of the GR gene and one polymorphism of the HSD11B1 gene. GR gene haplotypes were predicted based on genotyping results. Relapse-free survival, mortality, renal survival, metabolic adverse events and infections were compared between carriers and non-carriers of GR haplotypes and the HSD11B1 genotype.
Results. Carriers of haplotype 4 (ER22/23EK + 9 beta+Tthlll1) of GR had a significantly higher 5-year mortality risk [hazard ratio (HR) 4.5 (95% CI 1.6, 12.8)] and had a higher risk of developing end-stage renal disease [HR 7.4 (95% CI 1.9, 28.7)]. Carriers of a minor variant of HSD11B1 more frequently experienced relapse [HR 2.5 (95% CI 1.5, 4.1)] except if they also carried haplotype 1 (Bcll) of GR. Homozygous carriers of haplotype 1 had a higher risk of developing dyslipidaemia [HR 4.1 (95% CI 1.8, 9.6)]. The occurrence of infections did not differ between GR haplotypes and HSD11B1 genotypes.
Conclusion. Haplotypes 1 and 4 of GR and a polymorphism of the HSD11B1 gene were associated with clinically relevant inflammatory and metabolic outcomes in ANCA-associated vasculitis.
Original language | English |
---|---|
Pages (from-to) | 447-454 |
Number of pages | 8 |
Journal | Rheumatology |
Volume | 58 |
Issue number | 3 |
Early online date | 14-Nov-2018 |
DOIs | |
Publication status | Published - Mar-2019 |
Keywords
- anti-neutrophil cytoplasm antibody
- biomarkers
- epidemiology
- genetics
- inflammation
- metabolic disease
- microscopic polyangiitis
- vasculitis
- Wegener's granulomatosis
- CYCLOPHOSPHAMIDE TREATMENT
- IN-VIVO
- POLYMORPHISMS
- HAPLOTYPE
- SENSITIVITY
- RECOMMENDATIONS
- ER22/23EK
- SURVIVAL
- RELAPSE
- HEALTH