P686 Thiopurine methyltransferase polymorphism in Lithuanian inflammatory bowel disease patients

Abstract

Methods: We investigated 77 SNPs with moderate to strong association in five previously published genome-wide association studies of CD or UC, respectively. Our replication study comprised 447 Lithuanian and Latvian UC patients and 1,154 healthy controls. Single-marker case-control, genotypephenotype association, SNP-SNP epistasis analyses and metaanalysis were performed. Results: After correcting for multiple testing, we confirmed associations at 21q21.1 (rs1736135, P= 8.01×10 6), 6q21 (rs7746082, P= 6.41×10 5), JAK2 (rs10758669, P= 8.08×10 6), RNF186 (rs3806308, P= 2.40×10 6), and ORMDL3 (rs2872507, P= 1.24×10 6). Pooling our data with the original UC data substantiated four of the associations and revealed additional six loci to be associated with UC at genome-wide level (P< 5×10 8). No association with any disease subphenotype was found. SNP-SNP interaction analysis showed significant epistasis between SNPs in the PTPN22 (rs2476601) and C13orf31 (rs3764147) genes and increased risk for UC (P= 1.64×10 6, OR = 2.44). In silico prediction of the interactive network of these genes further validated a possible interaction. Conclusions:We confirmed the association of five loci (21q21.1, 6q21, JAK2, RNF186, and ORMDL3) with UC in the LithuanianLatvian population. SNP-SNP interaction analysis showed that the combination of SNPs in the PTPN22 (rs2476601) and C13orf31 (rs3764147) genes increase the risk for UC.