A risk haplotype in the Solute Carrier Family 22A4/22A5 gene cluster influences phenotypic expression of Crohn's disease

Abstract

Background & Aims: Previously, we identified 2 functionally relevant polymorphisms in the SLC22A4/22A5 genes at the IBD5 locus that alter gene/protein function and comprise a 2-allele haplotype (SLC22A-TC) associated with increased risk for Crohn's disease (CD). Here we examine the contribution of this susceptibility haplotype alone and in combination with CARD15 variants to CD subphenotypes and to susceptibility to ulcerative colitis (UC). Methods: Phenotype-genotype associations were evaluated in a Canadian cohort including 507 patients with CD, 216 patients with UC, and 352 ethnically matched controls genotyped for SLC22A4 C1672T, SLC22A5 G-207C, and the major CD-associated CARD15 variants. Results: The SLC22A-TC haplotype was strongly associated (P