Publication

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.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Hessels, A. C., Tuin, J., Sanders, J. S. F., Huitema, M. G., van Rossum, E. F. C., Koper, J. W., ... Rutgers, A. (2019). Clinical outcome in anti-neutrophil cytoplasmic antibody-associated vasculitis and gene variants of 11 beta-hydroxysteroid dehydrogenase type 1 and the glucocorticoid receptor. Rheumatology, 58(3), 447-454. https://doi.org/10.1093/rheumatology/key319

Author

Hessels, Arno C ; Tuin, Janneke ; Sanders, Jan Stephan F ; Huitema, Minke G ; van Rossum, Elisabeth F C ; Koper, Jan W ; van Beek, André P ; Stegeman, Coen A ; Rutgers, Abraham. / Clinical outcome in anti-neutrophil cytoplasmic antibody-associated vasculitis and gene variants of 11 beta-hydroxysteroid dehydrogenase type 1 and the glucocorticoid receptor. In: Rheumatology. 2019 ; Vol. 58, No. 3. pp. 447-454.

Harvard

Hessels, AC, Tuin, J, Sanders, JSF, Huitema, MG, van Rossum, EFC, Koper, JW, van Beek, AP, Stegeman, CA & Rutgers, A 2019, 'Clinical outcome in anti-neutrophil cytoplasmic antibody-associated vasculitis and gene variants of 11 beta-hydroxysteroid dehydrogenase type 1 and the glucocorticoid receptor', Rheumatology, vol. 58, no. 3, pp. 447-454. https://doi.org/10.1093/rheumatology/key319

Standard

Clinical outcome in anti-neutrophil cytoplasmic antibody-associated vasculitis and gene variants of 11 beta-hydroxysteroid dehydrogenase type 1 and the glucocorticoid receptor. / Hessels, Arno C; Tuin, Janneke; Sanders, Jan Stephan F; Huitema, Minke G; van Rossum, Elisabeth F C; Koper, Jan W; van Beek, André P; Stegeman, Coen A; Rutgers, Abraham.

In: Rheumatology, Vol. 58, No. 3, 03.2019, p. 447-454.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Hessels AC, Tuin J, Sanders JSF, Huitema MG, van Rossum EFC, Koper JW et al. Clinical outcome in anti-neutrophil cytoplasmic antibody-associated vasculitis and gene variants of 11 beta-hydroxysteroid dehydrogenase type 1 and the glucocorticoid receptor. Rheumatology. 2019 Mar;58(3):447-454. https://doi.org/10.1093/rheumatology/key319


BibTeX

@article{fc0672ec04f9444d840382d9098c048d,
title = "Clinical outcome in anti-neutrophil cytoplasmic antibody-associated vasculitis and gene variants of 11 beta-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 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.",
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",
author = "Hessels, {Arno C} and Janneke Tuin and Sanders, {Jan Stephan F} and Huitema, {Minke G} and {van Rossum}, {Elisabeth F C} and Koper, {Jan W} and {van Beek}, {Andr{\'e} P} and Stegeman, {Coen A} and Abraham Rutgers",
year = "2019",
month = "3",
doi = "10.1093/rheumatology/key319",
language = "English",
volume = "58",
pages = "447--454",
journal = "Rheumatology",
issn = "1462-0324",
publisher = "Oxford University Press",
number = "3",

}

RIS

TY - JOUR

T1 - Clinical outcome in anti-neutrophil cytoplasmic antibody-associated vasculitis and gene variants of 11 beta-hydroxysteroid dehydrogenase type 1 and the glucocorticoid receptor

AU - Hessels, Arno C

AU - Tuin, Janneke

AU - Sanders, Jan Stephan F

AU - Huitema, Minke G

AU - van Rossum, Elisabeth F C

AU - Koper, Jan W

AU - van Beek, André P

AU - Stegeman, Coen A

AU - Rutgers, Abraham

PY - 2019/3

Y1 - 2019/3

N2 - 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.

AB - 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.

KW - anti-neutrophil cytoplasm antibody

KW - biomarkers

KW - epidemiology

KW - genetics

KW - inflammation

KW - metabolic disease

KW - microscopic polyangiitis

KW - vasculitis

KW - Wegener's granulomatosis

KW - CYCLOPHOSPHAMIDE TREATMENT

KW - IN-VIVO

KW - POLYMORPHISMS

KW - HAPLOTYPE

KW - SENSITIVITY

KW - RECOMMENDATIONS

KW - ER22/23EK

KW - SURVIVAL

KW - RELAPSE

KW - HEALTH

U2 - 10.1093/rheumatology/key319

DO - 10.1093/rheumatology/key319

M3 - Article

C2 - 30445609

VL - 58

SP - 447

EP - 454

JO - Rheumatology

JF - Rheumatology

SN - 1462-0324

IS - 3

ER -

ID: 67593621