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.
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.
Authors: Tristan M Sissung; Sarah M Troutman; Tessa J Campbell; Heather M Pressler; Hyeyoung Sung; Susan E Bates; William D Figg Journal: Discov Med Date: 2012-01 Impact factor: 2.970
Authors: Kai Wang; Haitao Zhang; Subra Kugathasan; Vito Annese; Jonathan P Bradfield; Richard K Russell; Patrick M A Sleiman; Marcin Imielinski; Joseph Glessner; Cuiping Hou; David C Wilson; Thomas Walters; Cecilia Kim; Edward C Frackelton; Paolo Lionetti; Arrigo Barabino; Johan Van Limbergen; Stephen Guthery; Lee Denson; David Piccoli; Mingyao Li; Marla Dubinsky; Mark Silverberg; Anne Griffiths; Struan F A Grant; Jack Satsangi; Robert Baldassano; Hakon Hakonarson Journal: Am J Hum Genet Date: 2009-02-26 Impact factor: 11.025
Authors: K van der Weide; H Loovers; K Pondman; J Bogers; T van der Straaten; E Langemeijer; D Cohen; J Commandeur; J van der Weide Journal: Pharmacogenomics J Date: 2016-05-10 Impact factor: 3.550