Variations in the NRAMP1 Gene and Susceptibility to Tuberculosis in West Africans

Abstract

Background Genetic factors may affect the sus- ceptibility to tuberculosis, but no specific genes gov- erning susceptibility have been identified. In mice, natural resistance to infection with some mycobac- teria 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 polymor- phisms in NRAMP1 in a case–control study of tuber- culosis in the Gambia, West Africa. Methods Sequence-specific oligonucleotide hybrid- ization and microsatellite analysis were used to type NRAMP1 polymorphisms in 410 adults (mean age, 34.7 years) with smear-positive pulmonary tubercu- losis and 417 ethnically matched, healthy controls. Patients with human immunodeficiency virus infec- tion were excluded. Results Four NRAMP1 polymorphisms were each significantly associated with tuberculosis. Subjects who were heterozygous for two NRAMP1 polymor- phisms 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 ra- tio, 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. (N Engl J Med 1998;338:640-4.)