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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:628.)
© 2004 American Heart Association, Inc.

Brief Reviews

Genetic Testing for Cardiovascular Disease Susceptibility: A Useful Clinical Management Tool or Possible Misinformation?

Steve E. Humphries; Paul M. Ridker; Philippa J. Talmud

From Centre for Cardiovascular Genetics (S.E.H., P.J.T.), British Heart Foundation Laboratories, Rayne Building, Royal Free and University College London Medical School, London, UK; and The Centre for Cardiovascular Disease Prevention (P.M.R.), Divisions of Cardiovascular Diseases and Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Dr Philippa J. Talmud, Centre for Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories, Rayne Building, Royal Free and University College Medical School, 5 University St, London WC1E 6JF, UK. E-mail p.talmud{at}ucl.ac.uk

Genetic susceptibility tests are already advertised on the Internet to identify individuals at above average risk for cardiovascular disease (CVD), such as deep vein thrombosis, hyperlipidemia, or atherosclerosis, whereas other tests claim to predict response to a particular drug treatment. Some kits are available to the public directly, bypassing a doctor. Their value, however, must be considered carefully, because although a genotype may be strongly and consistently associated with an intermediate trait, and because the intermediate trait is a strong predictor of CVD risk, there may be little or no association of genotype with risk over and above that of the measured trait. This is because multigenic effects and environmental modification (context dependency) of genotype effects determine CVD risk. An individual’s personal characteristics and plasma risk-trait levels (which reflect both genotype and exposure) at present are the best predictors of clinical outcome. Only when genetic tests surpass this, possibly by the inclusion of many functional common variants, in conjunction with their context-dependent effects on risk, might their usefulness in clinical management be realized. Here we review some of the particular issues and concerns raised by CVD-risk genetic testing, and suggest areas of further research to address these issues.

Key Words: Factor V Leiden • ApoE • risk production • ROC curves

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