THE NATURAL RESISTANCE-ASSOCIATED MACROPHAGE PROTEIN GENE IS ASSOCIATED WITH CROHNS-DISEASE

Background. Identification of the genes causing inflammatory bowel dis ease (IBD) would enhance the understanding of and the treatment option s for this disease. A hyperreactive immune response toward the intesti nal flora has been implicated in the pathology of IBD. The natural res istance-associated macrophage protein (NRAMP) gene is believed to regu late macrophage function, especially the ability to fight intracellula r pathogens. Genetic differences of NRAMP might, therefore, be associa ted with IBD. Methods. True DNA markers (D2S434 and D2S1323) near NRAM P were polymerase chain reaction (PCR) amplified and genotyped with DN A from 103 patients with Crohn disease, 85 patients with ulcerative co litis, and 98 control subjects. Clinical data were obtained for all pa tients. Comparisons were made by chi-squared analysis. Disease associa tion 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 patie nts 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-onse t groups of patients with Crohn's disease (p = 0.05). Conclusions. Thi s study is the first to report an association between the NRAMP gene a nd Crohn's disease.