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

Arno C Hessels, Janneke Tuin, Jan Stephan F Sanders, Minke G Huitema, Elisabeth F C van Rossum, Jan W Koper, André P van Beek, Coen A Stegeman, Abraham Rutgers

OnderzoeksoutputAcademicpeer review

4 Citaten (Scopus)
2 Downloads (Pure)


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.

Originele taal-2English
Pagina's (van-tot)447-454
Aantal pagina's8
Nummer van het tijdschrift3
Vroegere onlinedatum14-nov.-2018
StatusPublished - mrt.-2019

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