Intended for healthcare professionals

Clinical Review Science, medicine, and the future

Susceptibility to infection

BMJ 2000; 321 doi: (Published 28 October 2000) Cite this as: BMJ 2000;321:1061
  1. Dominic Kwiatkowski, MRC clinical research professor. (
  1. Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN

    Genetic factors explain, at least in part, why some people resist infection more successfully than others. Rare gene disruptions cause fatal vulnerability to specific microbes, but more subtle differences are common and arise from minor variation in many genes. Recent advances in the human genome project and in high throughput genotyping technology will make it feasible within the next decade to screen the whole genome for genetic factors that determine susceptibility to HIV and AIDS, malaria, and tuberculosis. This will help to identify critical pathways of host defence and generate novel strategies for disease prevention. Understanding the evolutionary impact of infectious disease on the human genome may shed light on the origins of other common diseases, particularly those with an atopic or autoimmune component.

    Why study genetic susceptibility to infection?

    Historical accounts of the plague tell of individuals who survived unscathed in households where almost everyone else died. Each winter, British hospital wards are full of infants requiring oxygen therapy for bronchiolitis, but most infants infected with the same virus have little more than a runny nose. Over a million African children die each year of malaria, but many more remain in relatively good health despite being continually infected with the parasite.

    To what extent does our genetic make up determine the different ways that we respond to the same infectious agent? This is difficult to answer because of the many other contributory factors involved, such as previous health, acquired immunity, and variability in the pathogen. Epidemiological analysis of the genetic component is confounded by environmental factors that cause familial clustering and is further complicated by the many different genes that are likely to be involved. Nevertheless, there is compelling evidence for a genetic component, including twin studies of tuberculosis,1 leprosy,2 malaria,3 and Helicobacter pylori infection4 and a large survey that found …

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