The genetics of host resistance and susceptibility to tuberculosis

The study of human genomics has the potential to aid our understanding of the interindividual and interpopulation differences in susceptibility to tuberculosis. Resistance to infection is affected by the ability of macrophages to phagocytose and destroy the bacilli. Several genes are involved in this process, and two have been the focus of recent interest: the natural resistance-associated protein (NRAMP1) gene and the genes coding for the vitamin D receptor. Susceptibility genes have also been discovered--for example, one on the X chromosome that may explain the increased susceptibility of males to tuberculosis. Studies have also focused on the variations in virulence of the bacillus in both its drug-susceptible and drug-resistant forms. These mechanisms must be understood in order to prevent, or combat, the emergence of a virulent, multidrug-resistant form of the bacillus that would be uncontrollable by means of today's treatment strategies.