Search in the Abstract Database

Search Abstracts 2011

* = Presenting author

P364. Genetic analysis of multiple inflammatory bowel disease susceptibility markers in the Lithuanian and Latvian patient populations

J. Sventoraityte1, L. Kupcinskas1, G. Denapiene2, M. Leja3, A. Derovs3, J. Valantinas2, T. Balschun4, G. Kiudelis1, S. Schreiber4, A. Franke4

1Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania; 2Vilnius University, Vilnius, Lithuania; 3University of Latvia, Riga, Latvia; 4Institute of Clinical Molecular biology, Christian Albrecht's University, Kiel, Germany

Introduction and Objectives: Inflammatory bowel disease (IBD), a chronic gastrointestinal inflammatory disorder with a complex genetic background, most commonly presents as either one of the two subtypes, ulcerative colitis (UC) or Crohn's disease (CD). The number genetic variations conferring to IBD susceptibility increased over the past few years after the introduction of genome-wide association scans (GWAS). Although several susceptibility loci have been replicated, some of the associations have been reported to be unique for certain ethnicities.

Aims and Methods: To perform a comprehensive association analysis of genetic markers in the Lithuanian and Latvian IBD patient sample set. The large replication study was performed using 582 Lithuanian and Latvian IBD patients (139 CD and 443 UC) and 1157 controls. A set of 88 SNPs that showed moderate or strong associations with CD and/or UC in previous GWA studies were genotyped using SNPlex™ and TaqMan® genotyping technologies (Applied Biosystems, Foster City, USA). The SNPs were quality-controlled for: genotyping success rate (>90%), allele frequency (>1% in healthy controls), deviation from Hardy-Weinberg equilibrium (pHWE > 0.01 in the control sample). Assessment of all SNPs and single-marker association analysis were performed using the program PLINK. Nominal P-values were corrected for multiple-testing using a Bonferroni correction.

Results: Single-marker analysis revealed significant associations between CD and genetic variants of NOD2 gene: rs2066847 (pnom = 2.81×10−14, OR = 4.17 (95% CI: 2.81–6.18)) and rs2076756 (pnom = 2.74×10−9, OR = 2.24 (95% CI: 1.71–2.94)). In the UC group, we confirmed associations with JAK2 (rs10758669; pnom = 3.26×10−4, OR = 1.36 (95% CI: 1.15–1.60)) and RNF186 (rs3806308; pnom = 3.89×10−4, OR = 0.74 (95% CI: 0.63–0.87)); moreover we also identified associations with SNPs that in previous studies in other populations were associated only with CD phenotype: rs1736135 (21q21.1; pnom = 3.70×10−5, OR = 0.70 (95% CI: 0.59–0.83)) and rs7746082 (PRDM1; pnom = 9.49×10−5, OR = 1.42 (95% CI: 1.19–1.69)).

Conclusion: We replicated significant genetic associations for Crohn's disease with NOD2 gene; for ulcerative colitis with PRDM1, ORMDL3, 21q21.1, JAK2, RNF186 genes in the Lithuanian and Latvian IBD patient pool.