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Functional Variations of Organic Cation Transporters associated to Inflammatory Bowel Disease (IBD) in a Manitoba Cohort
Author(s) -
Eck Peter Karl,
Serrano Alejandra,
Yurkova Natasha,
Berstein Charles
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.109.6
Subject(s) - haplotype , single nucleotide polymorphism , inflammatory bowel disease , linkage disequilibrium , allele , ulcerative colitis , medicine , population , genotype , crohn's disease , gastroenterology , immunology , genetics , biology , disease , gene , environmental health
Polymorphisms in SLC22A4 , SLC22A23 and IBD5 locus have been associated with pathogenesis of IBD. This study sought to investigate the association of common and rare single nucleotide polymorphisms (SNPs) within those genes in Manitoba's IBD population. DNA samples from 160 patients with Crohn's Disease (CD), 149 patients with Ulcerative Colitis (UC) and 142 healthy controls were genotyped by PCR‐RFLP analysis. The IBD5 rs11739136‐C and rs17622208‐A alleles are associated with increased susceptibility to CD (OR=1.8, 95%CI 1.28–2.5, p=0.0006; OR=1.4, 95%CI 1.01–1.92, p=0.04, respectively). Moreover, rs11739136‐CC homozygosity increased the susceptibility of UC (OR=4.74, 95% CI 1.74–12.9, p=0.0009). Both CD (62%) and UC (64%) showed higher frequencies of SLC22A23 rs17309827 T allele than controls (61%). SLC22A4 rs1050152 showed strong Linkage Disequilibrium (LD) (D′ =0.98) with rs11739135. The risk alleles conform a haplotype (TACT) which is carried by 38.8% in CD patients and 29.8% in controls (p=0.02). We report that rs11739135 and rs17622208 best tag IBD5 haplotypes. Two selected rare polymorphisms in SLC22A4 (rs11568500 and rs11568510) were not detected in our population. Rare variations might be relevant in populations with different ethnical background. Further studies on the role of solute transporters in IBD are needed to develop therapeutic interventions.