��2 tests were applied to test for association of single nucleotide polymorphisms (SNPs) with disease, and the presence of MAP DNA. RESULTS: SLC11A1 Dasatinib manufacturer 1730G>A and SLC11A 1469+14G>C were not associated with CD, UC, or IBD. The SLC11A1 1730A minor allele was over-represented in patients who did not require immunomodulator therapy (P = 0.002, OR: 0.29, 95% CI: 0.13-0.66). The frequency of the SLC11A1 469+14C allele was higher in the subset of study participants who tested positive for MAP DNA (P = 0.02, OR: 1.56, 95% CI: 1.06-2.29). No association of SLC11A1 1730G>A with MAP was observed. CONCLUSION: Although SLC11A1 was not associated with IBD, association with MAP suggests that SLC11A1 is important in determining susceptibility to bacteria implicated in the etiology of CD.

Keywords: NRAMP1, Crohn��s disease, Ulcerative colitis, IS900 polymerase chain reaction INTRODUCTION The solute carrier family 11 (SLC11A1) gene (also known as natural resistance associated macrophage protein 1, NRAMP1)[1] has been associated with susceptibility to intracellular pathogens since its initial identification in mice[2]. SLC11A1 encodes a divalent cation transporter that is located in endosome and phagosome membranes[3] of macrophages and monocytes within the liver, spleen and lungs[2,4]. This transporter plays a key role in mounting an effective immune response against intracellular pathogens[1,5] through its involvement in the acidification of the phagosomes[6], as well as the regulation of nitric oxide, interleukin-10[7] and vacuolar iron concentrations[8].

Given the pivotal roles that SLC11A1 plays in innate immunity, it is not surprising that the relationship between polymorphisms in SLC11A1 and a number of autoimmune and mycobacterial diseases has been explored. Associations have been found with leprosy[9], tuberculosis[10], rheumatoid arthritis[11], visceral leishmaniasis[12], multiple sclerosis[13], type 1 diabetes mellitus[14], and inflammatory bowel disease (IBD)[15-18]. Most of these disease associations have been with a promoter dinucleotide microsatellite (GTn) that is known to affect SLC11A1 expression levels[19]. However, SLC11A1 also contains a number of single nucleotide polymorphisms (SNPs), including SLC11A1 1730G>A (rs17235409; D543N) and SLC11A1 469+14G>C (rs3731865; INT4G>C).

The non-synonymous SNP 1730G>A is thought to alter Drug_discovery the protein function[18], whereas the intronic SNP 469+14G>C has no known functional effect, but has been suggested to be in linkage disequilibrium with functional promoter polymorphisms[12]. SLC11A1 1730G>A and SLC11A1 469+14G>C have been tested for association with Crohn��s disease (CD) in two European cohorts. Although the smaller of the two studies found no association with CD, Gazouli et al[18] have reported a significant association of both SNPs with disease (SLC11A1 1730G>A Pgenotypic = 0.