VARIATIONS IN THE NRAMPI GENE AND SUSCEPTIBILITY TO TUBERCULOSIS IN WEST AFRICANS

Background Genetic factors may affect the susceptibility to tuberculos is, but no specific genes governing susceptibility have been identifie d. in mice, natural resistance to infection with some mycobacteria is influenced by the gene for natural-resistance-associated macrophage pr otein 1 (Nramp1), but the role of the human homologue of this gene, NR AMP1, in tuberculosis is unknown, We typed polymorphisms in NRAMP1 in a case-control study of tuberculosis in the Gambia, West Africa. Metho ds Sequence-specific oligonucleotide hybridization and microsatellite analysis were used to type NRAMP1 polymorphisms in 410 adults (mean ag e, 34.7 years) with smear-positive pulmonary tuberculosis and 417 ethn ically matched, healthy controls. Patients with human immunodeficiency virus infection were excluded. Results Four NRAMP1 polymorphisms were each significantly associated with tuberculosis, Subjects who were he terozygous for two NRAMP1 polymorphisms in intron 4 and the 3' untrans lated 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 NRAM P1 affects susceptibility to tuberculosis in West Africans. (C) 1998, Massachusetts Medical Society.