Natural resistance-associated macrophage protein 1 polymorphisms are associated with microscopy-positive tuberculosis.
The natural resistance-associated macrophage protein 1 (NRAMP1) is implicated in the pathophysiology of mycobacterial infections. We investigated by polymerase chain reaction previously published Nramp1 genotypes at 4 loci-INT4, N543D, 3'UTR, and 5'(CA)(n) microsatellite markers-in 104 human immunodeficiency virus-negative patients with tuberculosis and 176 healthy control subjects living in Denmark. No significant difference in genotype frequency was found between white patients with tuberculosis and control subjects (P>.16), but carriage of Nramp1 variant alleles at loci INT4 and 5'(CA)(n) conferred a significantly increased risk of having microscopy-positive compared with microscopy-negative tuberculosis (65% vs. 35% [P=.0004] and 63% vs. 38% [P=.047], respectively). The Nramp1 alleles were not associated with increased risk for the development of cavities seen on chest radiographs, or with extrapulmonary tuberculosis. These results indicate that variant alleles in the Nramp1 gene are associated with increased mycobacterial replication rather than susceptibility for tuberculosis and may thus confer increased risk of severe disease.
Department of Clinical Immunology, Tissue Typing Laboratory, Rigshospitalet, Denmark. cs@rh.dk
Christian
C
Søborg
Aase B
AB
Andersen
Hans O
HO
Madsen
Axel
A
Kok-Jensen
Peter
P
Skinhøj
Peter
P
Garred
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People; D044383:Black People; D027682:Cation Transport Proteins / Q000235:genetics*; D003718:Denmark / Q000208:ethnology; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008853:Microscopy / Q000379:methods; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D011110:Polymorphism, Genetic; D014397:Tuberculosis, Pulmonary / Q000208:ethnology / Q000235:genetics* / Q000382:microbiology; D044465:White People; D000099173:Natural Resistance-associated Macrophage Protein 1
D027682:Cation Transport Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1