Associations of allelic variants of the multidrug resistance gene (ABCB1 or MDR1) and inflammatory bowel disease and their effects on disease behavior: A case-control and meta-analysis study

Clive M. Onnie, Sheila A. Fisher, Reenal Pattni, Jeremy Sanderson, Alastair Forbes, Cathryn M. Lewis, Christopher G. Mathew

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Background: Allelic variants of the ATP-binding cassette, subfamily B member 1 (ABCB1), also known as the multidrug resistance gene (MDR1) that encodes the membrane-bound efflux transporter P-glycoprotein 170 (PGP-170), have been associated with inflammatory bowel disease but with conflicting results. Methods: The present study examined the association of ABCB1 C3435T and G2677T/A in a large British case-control cohort of 828 Crohn's disease, 580 ulcerative colitis (UC) cases, and 285 healthy controls. The effect of these variants was further examined with respect to phenotypic and epidemiological characteristics. A meta-analysis was carried out of our results and those from 8 previously published association studies of the C3435T variant in inflammatory bowel disease. Results: The 2677T allele was significantly increased in British UC cases compared with controls (45.2% vs. 39.6%; P = 0.034). In particular, the TT genotype was significantly associated with severe UC (odds ratio [OR] 1.90; 95% CI 1.01-3.55) and the use of steroids in UC (OR 1.77; 95% CI 1.08-2.88). No significant association was seen with C3435T and UC, Crohn's disease, or any clinical subgroup. A meta-analysis of 9 association studies of C3435T showed a significant association of the 3435T allele with UC (OR 1.12; 95% CI 1.02-1.23; P = 0.013) but not with CD. Conclusions: These results indicate that ABCB1 sequence variants are associated with a small increase in the risk of developing UC and may influence disease behavior.

Original languageEnglish
Pages (from-to)263-271
Number of pages9
JournalInflammatory Bowel Diseases
Volume12
Issue number4
DOIs
StatePublished - Apr 2006
Externally publishedYes

Keywords

  • Association
  • Crohn's disease
  • Genetics
  • Meta-analysis
  • Ulcerative colitis

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