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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.
- Source :
-
Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2019 Mar 01; Vol. 58 (3), pp. 447-454. - Publication Year :
- 2019
-
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.<br />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.<br />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.<br />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.<br /> (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Adult
Aged
Alleles
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis drug therapy
Disease-Free Survival
Female
Gene Frequency
Genotype
Haplotypes
Humans
Male
Middle Aged
Pharmacogenetics
Remission Induction
Treatment Outcome
11-beta-Hydroxysteroid Dehydrogenase Type 1 genetics
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis genetics
Glucocorticoids therapeutic use
Polymorphism, Single Nucleotide
Prednisolone therapeutic use
Receptors, Glucocorticoid genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1462-0332
- Volume :
- 58
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Rheumatology (Oxford, England)
- Publication Type :
- Academic Journal
- Accession number :
- 30445609
- Full Text :
- https://doi.org/10.1093/rheumatology/key319