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MDR1 gene polymorphisms are associated with ulcerative colitis in a cohort of Serbian patients with inflammatory bowel disease

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology in which genetic factors contribute to development of disease. Single nucleotide polymorphisms (SNPs) in multidrug resistance 1 (MDR1) gene encoding transporter P-glycoprotein have been associated with IBD, but the...

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Autores principales: Mijac, Dragana, Vukovic-Petrovic, Irena, Mijac, Vera, Perovic, Vladimir, Milic, Natasa, Djuranovic, Srdjan, Bojic, Daniela, Popovic, Dragan, Culafic, Djordje, Krstic, Miodrag, Jankovic, Goran, Pravica, Vera, Markovic, Milos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854418/
https://www.ncbi.nlm.nih.gov/pubmed/29543864
http://dx.doi.org/10.1371/journal.pone.0194536
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author Mijac, Dragana
Vukovic-Petrovic, Irena
Mijac, Vera
Perovic, Vladimir
Milic, Natasa
Djuranovic, Srdjan
Bojic, Daniela
Popovic, Dragan
Culafic, Djordje
Krstic, Miodrag
Jankovic, Goran
Pravica, Vera
Markovic, Milos
author_facet Mijac, Dragana
Vukovic-Petrovic, Irena
Mijac, Vera
Perovic, Vladimir
Milic, Natasa
Djuranovic, Srdjan
Bojic, Daniela
Popovic, Dragan
Culafic, Djordje
Krstic, Miodrag
Jankovic, Goran
Pravica, Vera
Markovic, Milos
author_sort Mijac, Dragana
collection PubMed
description BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology in which genetic factors contribute to development of disease. Single nucleotide polymorphisms (SNPs) in multidrug resistance 1 (MDR1) gene encoding transporter P-glycoprotein have been associated with IBD, but their role in disease susceptibility remains unclear. Therefore, the aim of this study was to investigate the association of three MDR1 polymorphisms, C1236T (rs1128503), G2677T/A (rs2032582) and C3435T (rs1045642), with Serbian IBD patients. METHODS: A total of 206 IBD patients, 107 Crohn's disease (CD) and 99 ulcerative colitis (UC), and 255 healthy controls were included in the study. All subjects were genotyped using TaqMan SNP genotyping assays. Comparisons between the groups were performed using the Pearson Chi-square test. False discovery rate according to Benjamini-Hochberg procedure was applied to adjust for multiple comparisons. RESULTS: Carriers of T allele of all three MDR1 SNPs were more common in UC patients compared to healthy controls, suggesting predisposing role of T allele of these SNPs in UC pathogenesis. Consistently, TT genotype of C1236T and TTT haplotype were also found more frequently in UC patients. On the other hand, C allele and CC genotype of C1236T and C3435T, as well as G allele and GG genotype of G2677T/A were more frequent in healthy subjects, implying protective role of these variants in UC. Likewise, CGC haplotype and CGC/CGC diplotype were more frequent in controls. Contrary to UC, no statistical difference was observed between CD patients and controls in any of the SNPs analyzed. CONCLUSION: MDR1 gene variants and haplotypes were associated with UC in Serbian IBD patients, further supporting their potential role in susceptibility to UC.
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spelling pubmed-58544182018-03-28 MDR1 gene polymorphisms are associated with ulcerative colitis in a cohort of Serbian patients with inflammatory bowel disease Mijac, Dragana Vukovic-Petrovic, Irena Mijac, Vera Perovic, Vladimir Milic, Natasa Djuranovic, Srdjan Bojic, Daniela Popovic, Dragan Culafic, Djordje Krstic, Miodrag Jankovic, Goran Pravica, Vera Markovic, Milos PLoS One Research Article BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology in which genetic factors contribute to development of disease. Single nucleotide polymorphisms (SNPs) in multidrug resistance 1 (MDR1) gene encoding transporter P-glycoprotein have been associated with IBD, but their role in disease susceptibility remains unclear. Therefore, the aim of this study was to investigate the association of three MDR1 polymorphisms, C1236T (rs1128503), G2677T/A (rs2032582) and C3435T (rs1045642), with Serbian IBD patients. METHODS: A total of 206 IBD patients, 107 Crohn's disease (CD) and 99 ulcerative colitis (UC), and 255 healthy controls were included in the study. All subjects were genotyped using TaqMan SNP genotyping assays. Comparisons between the groups were performed using the Pearson Chi-square test. False discovery rate according to Benjamini-Hochberg procedure was applied to adjust for multiple comparisons. RESULTS: Carriers of T allele of all three MDR1 SNPs were more common in UC patients compared to healthy controls, suggesting predisposing role of T allele of these SNPs in UC pathogenesis. Consistently, TT genotype of C1236T and TTT haplotype were also found more frequently in UC patients. On the other hand, C allele and CC genotype of C1236T and C3435T, as well as G allele and GG genotype of G2677T/A were more frequent in healthy subjects, implying protective role of these variants in UC. Likewise, CGC haplotype and CGC/CGC diplotype were more frequent in controls. Contrary to UC, no statistical difference was observed between CD patients and controls in any of the SNPs analyzed. CONCLUSION: MDR1 gene variants and haplotypes were associated with UC in Serbian IBD patients, further supporting their potential role in susceptibility to UC. Public Library of Science 2018-03-15 /pmc/articles/PMC5854418/ /pubmed/29543864 http://dx.doi.org/10.1371/journal.pone.0194536 Text en © 2018 Mijac et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Mijac, Dragana
Vukovic-Petrovic, Irena
Mijac, Vera
Perovic, Vladimir
Milic, Natasa
Djuranovic, Srdjan
Bojic, Daniela
Popovic, Dragan
Culafic, Djordje
Krstic, Miodrag
Jankovic, Goran
Pravica, Vera
Markovic, Milos
MDR1 gene polymorphisms are associated with ulcerative colitis in a cohort of Serbian patients with inflammatory bowel disease
title MDR1 gene polymorphisms are associated with ulcerative colitis in a cohort of Serbian patients with inflammatory bowel disease
title_full MDR1 gene polymorphisms are associated with ulcerative colitis in a cohort of Serbian patients with inflammatory bowel disease
title_fullStr MDR1 gene polymorphisms are associated with ulcerative colitis in a cohort of Serbian patients with inflammatory bowel disease
title_full_unstemmed MDR1 gene polymorphisms are associated with ulcerative colitis in a cohort of Serbian patients with inflammatory bowel disease
title_short MDR1 gene polymorphisms are associated with ulcerative colitis in a cohort of Serbian patients with inflammatory bowel disease
title_sort mdr1 gene polymorphisms are associated with ulcerative colitis in a cohort of serbian patients with inflammatory bowel disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854418/
https://www.ncbi.nlm.nih.gov/pubmed/29543864
http://dx.doi.org/10.1371/journal.pone.0194536
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