title: The -237C-->T promoter polymorphism of the SLC11A1 gene is associated with a protective effect in relation to inflammatory bowel disease in the South African population.
abstract: The purpose of this study was to assess the likelihood that variation in the promoter region of the solute carrier family 11 member 1 gene (SLC11A1) contributes to inflammatory bowel disease (IBD) susceptibility in the South African population. The study cohort included 102 IBD patients, 47 with Crohn's disease (CD) and 55 with ulcerative colitis, and 192 population-matched controls. Mutation analysis revealed two novel alleles for the 5'-(GT)n repeat polymorphism, t(gt)5ac(gt)5ac(gt)6ggcaga(g)6 (allele 8) and t(gt)5ac(gt)5ac(gt)8ggcaga(g)6 (allele 9), and one previously documented point mutation -237C-->T. A significantly decreased frequency of the -237C-->T promoter polymorphism was observed in the patient group with IBD (p<0.001) and CD (p<0.0006) compared with the population-matched control group. These findings may be related to previous in vitro studies, which demonstrated that the point mutation at nucleotide position -237 represents a functional polymorphism that affects regulation of the upstream 5'-(GT)n repeat polymorphism differentially upon iron loading. Our findings raise the possibility that iron dysregulation mediated by allelic effects of SLC11A1 may contribute to IBD susceptibility.
authors.affiliation: Department of Genetics, University of Stellenbosch, Stellenbosch, South Africa. mjulies@sun.ac.za
authors.forename: Monique G
authors.initials: MG
authors.lastname: Zaahl
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Winter
authors.forename: Louise
authors.initials: L
authors.lastname: Warnich
authors.forename: Maritha J
authors.initials: MJ
authors.lastname: Kotze
mesh_terms: D044383:Black People; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007501:Iron / Q000378:metabolism; D008297:Male; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D013019:South Africa; D044465:White People; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D007501:Iron; D000099173:Natural Resistance-associated Macrophage Protein 1