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

Dragana Mijac; Irena Vukovic-Petrovic; Vera Mijac; Vladimir Perovic; Natasa Milic; Srdjan Djuranovic; Daniela Bojic; Dragan Popovic; Djordje Culafic; Miodrag Krstic; Goran Jankovic; Vera Pravica; Milos Markovic

doi:10.1371/journal.pone.0194536

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

PLoS One. 2018 Mar 15;13(3):e0194536. doi: 10.1371/journal.pone.0194536. eCollection 2018.

Authors

Affiliations

¹ Clinic for Gastroenterology and Hepatology, Faculty of Medicine, University of Belgrade, Clinical Center of Serbia, Belgrade, Serbia.
² Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
³ Department for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
⁴ Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States of America.
⁵ Department of Gastroenterology, University Hospital Zvezdara, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B / genetics
Adult
Aged
Case-Control Studies
Colitis, Ulcerative / genetics*
Crohn Disease / genetics
Female
Gene Frequency
Genetic Predisposition to Disease*
Haplotypes / genetics
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Serbia
Young Adult

Substances

ABCB1 protein, human
ATP Binding Cassette Transporter, Subfamily B

Grants and funding

This study was supported by the Fund of The Serbian Ministry of Education, Science and Technological Development (Grant No 175038). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.