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

Abstract

OBJECTIVES:

We aimed to investigate whether five potential functional haplotypes of the glucocorticoid receptor (GR) gene and a single-nucleotide polymorphism of 11β-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 + 9β+TthIII1) 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 (BclI) 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.

• Authors: 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
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 58 Issue 3 Pg. 447-454 (03 01 2019) ISSN: 1462-0332 [Electronic] England
• PMID: 30445609 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Glucocorticoids
• Receptors, Glucocorticoid
• Prednisolone
• 11-beta-Hydroxysteroid Dehydrogenase Type 1
• HSD11B1 protein, human

Topics

• 11-beta-Hydroxysteroid Dehydrogenase Type 1 (genetics)
• Adult
• Aged
• Alleles
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis (drug therapy, genetics)
• Disease-Free Survival
• Female
• Gene Frequency
• Genotype
• Glucocorticoids (therapeutic use)
• Haplotypes
• Humans
• Male
• Middle Aged
• Pharmacogenetics
• Polymorphism, Single Nucleotide
• Prednisolone (therapeutic use)
• Receptors, Glucocorticoid (genetics)
• Remission Induction
• Treatment Outcome