Original Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Aug 21, 2010; 16(31): 3888-3896
Published online Aug 21, 2010. doi: 10.3748/wjg.v16.i31.3888
Glucocorticoid receptor gene haplotype structure and steroid therapy outcome in IBD patients
Jessica Mwinyi, Christa Wenger, Jyrki J Eloranta, Gerd A Kullak-Ublick
Jessica Mwinyi, Christa Wenger, Jyrki J Eloranta, Gerd A Kullak-Ublick, Division of Clinical Pharmacology and Toxicology, University Hospital, CH-8091 Zurich, Switzerland
Author contributions: Kullak-Ublick GA, Eloranta JJ and Wenger C designed the study; Wenger C and Eloranta JJ performed the laboratory experiments; Mwinyi J performed the sequence and statistical analysis; Mwinyi J, Eloranta JJ and Kullak-Ublick GA wrote the manuscript.
Supported by The Swiss IBD Cohort Study (SNF Grant 33CSC0-108792); the Swiss National Science Foundation (Grant 32-120463/1); the Zurich University Research Priority Programme “Integrative Human Physiology” (ZIHP); the Center of Clinical Research at the University Hospital Zurich; and the Novartis Foundation for Biomedical Research
Correspondence to: Gerd Kullak-Ublick, Professor, Division of Clinical Pharmacology and Toxicology, University Hospital, CH-8091 Zurich, Switzerland. gerd.kullak@usz.ch
Telephone: +41-44-2552068 Fax: +41-44-2554411
Received: March 11, 2010
Revised: May 14, 2010
Accepted: May 21, 2010
Published online: August 21, 2010
Abstract

AIM: To study whether the glucocorticoid receptor (GR/NR3C1) gene haplotypes influence the steroid therapy outcome in inflammatory bowel disease (IBD).

METHODS: We sequenced all coding exons and flanking intronic sequences of the NR3C1 gene in 181 IBD patients, determined the single nucleotide polymorphisms, and predicted the NR3C1 haplotypes. Furthermore, we investigated whether certain NR3C1 haplotypes are significantly associated with steroid therapy outcomes.

RESULTS: We detected 13 NR3C1 variants, which led to the formation of 17 different haplotypes with a certainty of > 95% in 173 individuals. The three most commonly occurring haplotypes were included in the association analysis of the influence of haplotype on steroid therapy outcome or IBD activity. None of the NR3C1 haplotypes showed statistically significant association with glucocorticoid therapy success.

CONCLUSION: NR3C1 haplotypes are not related to steroid therapy outcome.

Keywords: Inflammatory bowel disease; Steroid therapy; Glucocorticoid receptor; Pharmacogenetics; Haplotype analysis