Genetics and pulmonary medicine. 3. Genetic susceptibility to tuberculosis in human populations.

Abstract

Prior to the discovery of the tubercle bacillus, the observation that tuberculosis frequently occurred in many members of the same family convinced physicians that it was a hereditary disease.1 However, in 1882 when Robert Koch demonstrated that tuberculosis was caused by a microorganism,2attention turned to the importance of the pathogen and the genetic constitution of the host was largely ignored. It is estimated that only 10% of those who become infected with Mycobacterium tuberculosis will ever develop clinical disease,3 and in only a few cases is there an obvious identifiable risk factor such as diabetes, advanced age, alcohol abuse, HIV infection, or corticosteroid usage. Why then do some people succumb to the disease when most of the population can successfully fight off the tubercle bacillus? Clearly, although M tuberculosis is necessary, it is not sufficient. Determining why only some individuals are susceptible to tuberculosis is important as this will give us insight into which components of disease pathogenesis are important and hopefully assist the development of new treatment or prevention strategies. It is a common misapprehension that death from multifactorial diseases such as cancer and cardiovascular problems are influenced by genetic factors, but that death from infection is due to a bad environment or simply bad luck. In fact, a study of 960 adoptees in Denmark concluded that the genetic component of susceptibility to premature death from infectious diseases is greater than for cancer or cardiovascular causes.4 In 1949 the pioneering geneticist J B S Haldane recognised that infectious diseases have been the main agent of natural selection during the past 5000 years.5 Organisms which are widespread in the human population and which exert a high mortality will exert the most pronounced evolutionary effects.6 In the early part of the 19th century it …