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Clinical outcome in anti-neutrophil cytoplasmic antibody-associated vasculitis and gene variants of 11 beta-hydroxysteroid dehydrogenase type 1 and the glucocorticoid receptor

Hessels, 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.

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  • Clinical outcome in anti-neutrophil cytoplasmic antibody–associated vasculitis and gene variants of 11β-hydroxysteroid dehydrogenase type 1 and the glucocorticoid receptor

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DOI

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 languageEnglish
Pages (from-to)447-454
Number of pages8
JournalRheumatology
Volume58
Issue number3
Early online date14-Nov-2018
Publication statusPublished - 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

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