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
Two DNA markers (D2S434 and D2S1323) near NRAMP were polymerase chain reaction (PCR) amplified and genotyped with DNA from 103 patients with Crohn's 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's disease and control groups (p = 0.024). Two individual haplotypes of the patients with Crohn's 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.
Hofmeister
A
A
Price Institute of Surgical Research, Department of Surgery, University of Louisville School of Medicine, Ky., USA.
Neibergs
H L
HL
Pokorny
R M
RM
Galandiuk
S
S
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D027682:Cation Transport Proteins; D016001:Confidence Intervals; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007422:Intestines / Q000473:pathology; D033862:Iron-Binding Proteins; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012016:Reference Values; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D005819:Genetic Markers; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2