caa a22 4500 445887990 CHVBK 20180317145605.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s00535-011-0426-6 doi (NATIONALLICENCE)springer-10.1007/s00535-011-0426-6 Haplotype in the IBD5 region is associated with refractory Crohn's disease in Slovenian patients and modulates expression of the SLC22A5 gene [Elektronische Daten] [Katja Repnik, Uroš Potočnik] Background: The IBD5 locus (OMIM ID606348) on chromosome 5 was suggested to be one of the most important genetic factors involved in the pathogenesis of inflammatory bowel diseases (IBDs). However the main contributor from this region is still unknown. Methods: We investigated the possible association of the IBD5 locus with IBD in Slovenian patients and correlation between disease-associated single nucleotide polymorphisms (SNPs) and quantitative gene expression (eQTL) of candidate genes from the IBD5 locus in peripheral blood lymphocytes and colon tissue biopsies from IBD patients. We genotyped SNPs from the IBD5 locus in 312 healthy controls and 632 IBD patients. Results: We found statistically significant association of polymorphisms rs1050152 in gene SLC22A4 (p=0.005, OR=2.177, 95% CI=1.270-3.526) and rs2631372 in gene SLC22A5 (p=0.001, OR=0.473, 95% CI=0.307-0.731) and TC haplotype of both polymorphisms (p=0.006, OR=1,541, 95% CI=1.130-2.100) with refractory Crohn's disease (CD) in Slovenian patients who do not respond to standard therapy, including patients who develop fistulas. We found decreased expression of SLC22A4 and SLC22A5 genes in peripheral blood lymphocytes from IBD patients compared to control group and decreased expression of SLC22A5 gene in inflamed tissue biopsies compared to noninflamed colon (p=0.009). We found lower expression of SLC22A5 gene in IBD patients with disease-susceptible genotypes for both disease-associated SNPs. Conclusions: Our data suggest that SNPs and haplotype in the IBD5 SLC22A4/SLC22A5 region contribute to the development of particularly refractory Crohn's disease in the Slovenian population, and expression studies in blood lymphocytes and colon tissue biopsies and eQTL analysis suggest that SLC22A5 is the main gene in the IBD5 region contributing to the IBD pathogenesis. Springer, 2011 Inflammatory bowel disease nationallicence IBD5 nationallicence Expression quantitative trait locus (eQTL) nationallicence Repnik Katja Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Slomškov trg 15, 2000, Maribor, Slovenia aut Potočnik Uroš Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Slomškov trg 15, 2000, Maribor, Slovenia aut Journal of Gastroenterology Springer Japan 46/9(2011-09-01), 1081-1091 0944-1174 46:9<1081 2011 46 535 https://doi.org/10.1007/s00535-011-0426-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00535-011-0426-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Repnik Katja Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Slomškov trg 15, 2000, Maribor, Slovenia aut NATIONALLICENCE 700 1- Potočnik Uroš Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Slomškov trg 15, 2000, Maribor, Slovenia aut NATIONALLICENCE 773 0- Journal of Gastroenterology Springer Japan 46/9(2011-09-01), 1081-1091 0944-1174 46:9<1081 2011 46 535 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer