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Am Fam Physician. 2004;69(2):423

Genetic variations have been associated with disease susceptibility and disease outcomes. The association of asthma and allergy with certain gene polymorphisms or mutations is a common example of genetically determined disease susceptibility. The behavior and clinical manifestations of infectious diseases also might be dictated by the same phenomenon. Somech and associates reviewed the role of less common gene variants in susceptibility to infectious agents.

Human leukocyte antigen polymorphism is a known contributor to a growing list of diseases. Other genetic polymorphisms also alter the immune system or cause a deficiency or insufficiency of components of the immune system. Primary immunodeficiency diseases caused by genetic polymorphisms are now largely diagnosable with molecular probes. These disorders are classified as T lymphocyte, B lymphocyte, phagocytic cell, and complement deficiencies. All predispose to infection.

Less common genetic variants that alter host defense and predispose persons to specific infections result in other variations of the innate immune system (the first-line host defense of multicellular organisms) and the adaptive components of the immune system. Examples of some less common forms of gene alteration include: (1) XLP disease, a severe form of Epstein-Barr virus infection, (2) disseminated atypical Mycobacterium resulting from abnormalities in the interferon-gamma mediated immune pathway, (3) malaria susceptibility, (4) Ascaris burden in infected persons, (5) progression of liver disease in chronic hepatitis C virus, (6) susceptibility to recurrent acute otitis media, and (7) severity of response to group A streptococcus infection. Genetic variants also can contribute to increased risk of sepsis and poor outcome.

The authors conclude that host genetic variants play an important role in determining susceptibility to infectious disease and outcome of infection. Some variations may be protective, such as occurs in patients with malaria and hemoglobinopathies. Understanding the molecular basis of these variants may improve therapies and allow for development of useful vaccines. Future research might permit formulation of individualized risk profiles for a variety of infections, resulting in optimized treatments.

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