Interaction between IL23R gene and IBD5 locus in Hungarian ulcerative colitis patients

In previous single-locus association studies, the IBD5 loci were found not to confer susceptibility to UC, while the rs2201841 and rs1004819 IL23R were not investigated in Hungarian UC patients. The aim of our current work was to study two IL23R SNPs (rs1004819 and rs2201841) in Hungarian UC population and to test for possible statistical interaction, stratifying the IL23R genotypes by IBD5 genotypes. 320 unrelated subjects with ulcerative colitis and 316 healthy controls were genotyped. Interactions and specific genotype combinations of a total of seven variants were tested. The variants of IBD5 locus (IGR2198a_1 rs11739135, IGR2096a_1 rs12521868, IGR2230a_1 rs17622208 and SLC22A5 rs2631367) and IL23R (rs1004819, rs2201841) gene were genotyped by PCR-RFLP, the SLC22A4 rs1050152 was determined by direct sequencing. For the IL23R rs1004819 A allele we found significantly higher allele frequency (P = 0.032) in UC patients compared to control subjects. The SNP rs1004819 showed significant association with UC risk for carriers (P = 0.004, OR = 1.606; 95% CI:1.160 – 2.223) and the SNP rs2201842 for homozygotes (P = 0.030, OR = 1.983; 95% CI:1.069 – 3.678). There was no evidence for statistical interaction between IBD5 loci and IL23R genes using logistic regression analysis. After genotype stratification, we could detect a positive association on the background of rs1004819 A allele for SLC22A4 T allele, SLC22A5 C, IGR2198a_1 C or IGR2096_a T allele, the highest OR was calculated in the presence of SLC22A4 T allele (P = 0.005, OR = 2.015; 95% CI:1.230 – 3.300). There was no association with UC for any combinations of rs1004819 and IGR2230a_1. The IL23R rs2201841 homozygous genotype and IBD5 carrier status together did not confer susceptibility for ulcerative colitis. The present study has shown that UC susceptibility genes are likely to act in a complex interactive manner similar to CD.