Interaction of Genetic and Environmental Factors Causing Atherosclerosis by Immunologic Mechanisms

  • John D. Mathews
Conference paper


Animal experiments support epidemiologic evidence for the view that the immune response to autoantigens or to environmental antigens can cause human atherosclerosis. Some environmental factors (including infections, vasectomy) could cause atherosclerosis by contributing to autoimmunity in genetically susceptible individuals; infections and dietary factors could also cause atherosclerosis by providing “extrinsic” antigens. Human antibody responses to influenza and polio virus antigens are higher in individuals with high levels of plasma cholesterol, and plasma cholesterol levels increase during the course of the immune response. Immunogenetic loci (including Gm, HLA and possibly ABO blood groups) affect the immune response to particular environmental antigens and auto-antigens, and have been shown to be correlated with the risk of atherosclerotic disease in individuals. A model is proposed for genetic-environmental interactions causing coronary heart disease (CHD); geographical gradients in the frequencies of immunogenetic alleles are attributed to past natural selection by infectious agents; the pattern of correlation of CHD death rates with genetic gradients leads to the conclusion that (similar) infectious agents are still active as causes of CHD. A prediction of the hypothesis that environmental agents interact with immunogenetic alleles to cause cardiovascular disease has been successfully tested by showing that among patients presenting with acute myocardial infarction, individuals with similar HLA phenotypes tend to be affected at similar times.


Blood Group Environmental Agent Coronary Heart Disease Death Ethinyl Oestradiol Environmental Antigen 
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© Springer-Verlag New York Inc. 1980

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  • John D. Mathews

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