Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans

Abstract

Background: Genetic factors may affect the susceptibility to tuberculosis, but no specific genes governing susceptibility have been identified. In mice, natural resistance to infection with some mycobacteria is influenced by the gene for natural-resistance-associated macrophage protein 1 (Nramp1), but the role of the human homologue of this gene, NRAMP1, in tuberculosis is unknown. We typed polymorphisms in NRAMP1 in a case-control study of tuberculosis in the Gambia, West Africa.

Methods: Sequence-specific oligonucleotide hybridization and microsatellite analysis were used to type NRAMP1 polymorphisms in 410 adults (mean age, 34.7 years) with smear-positive pulmonary tuberculosis and 417 ethnically matched, healthy controls. Patients with human immunodeficiency virus infection were excluded.

Results: Four NRAMP1 polymorphisms were each significantly associated with tuberculosis. Subjects who were heterozygous for two NRAMP1 polymorphisms in intron 4 and the 3' untranslated region of the gene were particularly overrepresented among those with tuberculosis, as compared with those with the most common NRAMP1 genotype (odds ratio, 4.07; 95 percent confidence interval, 1.86 to 9.12; chi-square= 14.58; P<0.001).

Conclusions: Genetic variation in NRAMP1 affects susceptibility to tuberculosis in West Africans.

PIP: The authors typed polymorphisms in the human gene for natural-resistance-associated macrophage protein 1 (NRAMP1) in a case-control study of tuberculosis (TB) in the Gambia to determine whether genetic factors affect human susceptibility to TB. Sequence-specific oligonucleotide hybridization and microsatellite analysis were used to type NRAMP1 polymorphisms in 410 adults over age 16 years (mean age, 34.7 years) with smear-positive pulmonary TB and 417 ethnically matched, healthy controls. HIV-infected patients were excluded. 4 NRAMP1 polymorphisms were each significantly associated with TB. Subjects heterozygous for two NRAMP1 polymorphisms in intron 4 and the 3' untranslated region of the gene were especially overrepresented among those with TB, compared with those with the most common NRAMP1 genotype. It may therefore be concluded that genetic variation in NRAMP1 affects susceptibility to TB in West Africans.