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

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.