Clinical-alimentary tractAllelic variations of the multidrug resistance gene determine susceptibility and disease behavior in ulcerative colitis
Section snippets
Patients
This study was approved by the Lothian Research and Ethics Committee, and written consent was obtained from all patients. A total of 335 patients with UC and 268 with CD were recruited from the Lothian region (Scotland). The diagnosis of IBD was determined by standard clinical, radiologic, endoscopic, and histologic criteria.
Table 1, Table 2 summarize the clinical characteristics of patients studied. The median ages at diagnosis of UC and CD were 35.0 years (interquartile range, 25.3–50.3
Effect of MDR1 C3435T and G2677T polymorphism on overall disease susceptibility
Both the T allele and TT genotype of the MDR1 3435 SNP were significantly increased in patients with UC (58.2% vs 52.8%; P = .02; OR, 1.28; 95% CI, 1.03–1.58) compared with healthy controls (34.6% vs 26.5%; P = .04; OR, 1.60; 95% CI, 1.04–2.44) (Table 3). No significant differences in allele or genotype frequencies were seen in patients with CD (53.0% vs 52.8% [P = .43] and 26.9% vs 26.5% [P = .81], respectively) when compared with controls. A trend toward higher T-allele and genotype
Discussion
This study firstly provides replicated confirmation for the association of the MDR1 C3435T SNP with UC. In addition, we have made novel observations with respect to genotype-phenotype correlations, notably the strong association of the C3435T SNP with extensive UC. Finally, the haplotypic analyses involving C3435T and G2677T SNPs provide further new insights into the complexities of the contribution of the MDR1 gene; both protective and susceptible haplotypes were identified.
Indeed, in view of
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Multidrug resistance Gene-1 polymorphisms (C3435T and G2677T) and the risk of inflammatory bowel disease in Egyptian patients
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2019, Journal of Pharmaceutical SciencesCitation Excerpt :The best described ABC transporter in context with UC is ABCB1 (P-gp, ABCB1). Some genetic variants were suggested to be associated with UC susceptibility in humans.17-20 The important role of ABCB1 in UC was shown by the observation that abcb1a/b knockout mice develop an UC-like phenotype21 and further supported by the decreased ABCB1 expression in UC and CD patients compared with the control group.9,22
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- 1
G.-T.H. is supported by the Chief Scientist Office, Scottish Executive, United Kingdom
- 2
E.R.N. and H.D. are supported by the Wellcome Trust, United Kingdom.