Clinical outcome in anti-neutrophil cytoplasmic antibody-associated vasculitis and gene variants of 11 beta-hydroxysteroid dehydrogenase type 1 and the glucocorticoid receptorHessels, A. C., Tuin, J., Sanders, J. S. F., Huitema, M. G., van Rossum, E. F. C., Koper, J. W., van Beek, A. P., Stegeman, C. A. & Rutgers, A., Mar-2019, In : Rheumatology. 58, 3, p. 447-454 8 p.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||8|
|Early online date||14-Nov-2018|
|Publication status||Published - Mar-2019|
- 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