P664. Association between genetic markers related to tight junctions and inflammatory bowel disease
E. Norén1,2, S. Almer3,4, J. Söderman1, 1Ryhov County Hospital, Division of Medical Diagnostics, Jönköping, Sweden, 2Linköping University, Department of Clinical and Experimental Medicine, Linköping, Sweden, 3Karolinska Institutet, Department of medicine, Stockholm, Sweden, 4Karolinska University Hospital, GastroCentrum, Stockholm, Sweden
An increased intestinal permeability has been described in inflammatory bowel disease (IBD) patients and their relatives, which might indicate hereditary factors. Therefore, genes encoding tight junction (TJ) proteins should be considered functional candidate genes for IBD. In this study we aimed to elucidate a possible genetic influence of TJ-components on IBD-susceptibility, using a genetic association study based on single nucleotide polymorphism (SNP) markers in the genetic regions of F11R (1q21.2-q21.3), PARD3 (10p11.21), MAGI1 (3p14.1), MAGI2 (7q21), MAGI3 (1p12-p11.2), and PTEN (10q23.3).
Adult Swedish patients with IBD (n = 288), Crohn's disease (CD; n = 133) or ulcerative colitis (UC; n = 155) were included. Samples from an anonymized regional DNA bank consisting of randomly selected Swedish subjects were used as controls. Six genes were genotyped for 61 SNP markers using TaqMan OpenArray technique (Applied Biosystems). Allelic associations to disease were investigated by performing a case–control study. Using a chi-square test P < 0.05 (not corrected for multiple testing) was considered significant.
Significant associations were obtained between IBD overall and SNP markers in the genetic regions of MAGI3 (P = 0.002), MAGI2 (P = 0.010), F11R (P = 0.019), and MAGI1 (P = 0.024). Markers in the genetic regions of MAGI2 (P = 0.011) and MAGI1 (P = 0.037) were significantly associated with CD. Additionally, markers in the genetic regions of MAGI3 (P = 0.003), MAGI2 (P = 0.010), and F11R (P = 0.026) showed significant associations to UC.
Four out of six investigated TJ-related genes showed association to IBD overall as well as CD and UC. Our findings add further support for a genetically impaired intestinal epithelial barrier as one predisposing factor in the etiology of IBD. In-depth exploration of these TJ-components, may lead to a better understanding of the pathogenic mechanisms underlying IBD.
- Posted in: Poster presentations: Genetics (2014)