The natural resistance-associated macrophage protein gene is associated with Crohn's disease

Background. Identification of the genes causing inflammatory bowel disease (IBD) would enhance the understanding of and the treatment options for this disease. A hyperreactive immune response toward the intestinal flora has been implicated in the pathology of IBD. The natural resistance-associated macrophage protein (NRAMP) gene is believed to regulate macrophage function, especially the ability to fight intracellular pathogens. Genetic differences of NRAMP might, therefore, be associated with IBD. Methods. True DNA markers (D2S434 and D2S1323) near NRAMP were polymerase chain reaction (PCR) amplified and genotyped with DNA from 103 patients with Crohn disease, 85 patients with ulcerative colitis, and 98 control subjects. Clinical data were obtained for all patients. Comparisons were made by chi-squared analysis. Disease association with significant haplotypes was expressed as odds ratio. Results. Allele and genotype distributions were similar for both markers among all groups. Haplotype frequencies were different among Crohn disease and control groups (p = 0.024). Two individual haplotypes of the patients with Crohn disease were significant compared with control subjects: DA (p = 0.023; odds ratio, 0.5; 95% confidence interval, 0.3 to 0.9) and EA (p = 0.001; odds ratio, 3.5; 95% confidence interval, 1.6 to 3.2). The haplotype distribution was different within three age-of-onset groups of patients with Crohn's disease (p = 0.05). Conclusions. This study is the first to report an association between the NRAMP gene and Crohn's disease.