European Journal of Clinical Pharmacology

, Volume 63, Issue 10, pp 917–925

Possible role of MDR1 two-locus genotypes for young-age onset ulcerative colitis but not Crohn’s disease

  • T. Fiedler
  • C. Büning
  • W. Reuter
  • G. Pitre
  • E. Gentz
  • HH. Schmidt
  • J. Büttner
  • J. Ockenga
  • T. Gerloff
  • C. Meisel
  • H. Lochs
  • I. Roots
  • K. Köpke
  • A. Johne
Pharmacogenetics

Abstract

Background

The role of the single nucleotide polymorphisms (SNPs) on positions 2677G>T/A and 3435C>T of the multi-drug-resistance gene 1 (MDR1) in inflammatory bowel disease (IBD) remains unclear.

Aims

To further elucidate the potential impact of MDR1 two-locus genotypes on susceptibility to IBD and disease behaviour.

Patients and methods

Three hundred eighty-eight German IBD patients [244 with Crohn’s disease (CD), 144 with ulcerative colitis (UC)] and 1,005 German healthy controls were genotyped for the two MDR1 SNPs on positions 2677G>T/A and 3435C>T. Genotype–phenotype analysis was performed with respect to disease susceptibility stratified by age at diagnosis as well as disease localisation and behaviour.

Results

Genotype distribution did not differ between all UC or CD patients and controls. Between UC and CD patients, however, we observed a trend of different distribution of the combined genotypes derived from SNPs 2677 and 3435 (χ2 = 15.997, df = 8, p = 0.054). In subgroup analysis, genotype frequencies between UC patients with early onset of disease and controls showed significant difference for combined positions 2677 and 3435 (χ2 = 16.054, df = 8, p = 0.034 for age at diagnosis ≥25, lower quartile). Herein the rare genotype 2677GG/3435TT was more frequently observed (odds ratio = 7.0, 95% confidence interval 2.5 – 19.7). In this group severe course of disease behaviour depended on the combined MDR1 SNPs (χ2 = 16.101, df = 6, p = 0.017 for age at diagnosis ≥25). No association of MDR1 genotypes with disease subgroups in CD was observed.

Conclusions

While overall genotype distribution did not differ, combined MDR1 genotypes derived from positions 2677 and 3435 are possibly associated with young age onset of UC and severe course of disease in this patient group.

Keywords

MDR1 P-glycoprotein Inflammatory bowel disease Crohn’s disease Ulcerative colitis 

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • T. Fiedler
    • 1
  • C. Büning
    • 1
  • W. Reuter
    • 1
  • G. Pitre
    • 1
  • E. Gentz
    • 1
  • HH. Schmidt
    • 1
  • J. Büttner
    • 1
  • J. Ockenga
    • 1
  • T. Gerloff
    • 2
  • C. Meisel
    • 2
  • H. Lochs
    • 1
  • I. Roots
    • 2
  • K. Köpke
    • 2
  • A. Johne
    • 2
  1. 1.Department of Gastroenterology, Hepatology & EndocrinologyCharité – Universitätsmedizin BerlinBerlinGermany
  2. 2.Institute of Clinical PharmacologyCharité – Universitätsmedizin BerlinBerlinGermany

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