Clinical Review Science, medicine, and the future

Genetics and cardiovascular risk

BMJ 2001; 323 doi: (Published 15 December 2001) Cite this as: BMJ 2001;323:1409
  1. Ian N M Day, professor of human genetics (,
  2. David I Wilson, professor of human developmental genetics
  1. Human Genetics Division, Duthie Building (Mp808), Southampton University Hospital, Southampton SO16 6YD
  1. Correspondence to: I Day

    Cardiovascular disease is the commonest cause of death in the Western world, and congenital heart disease affects almost 1% of liveborn infants. Both diseases have substantial genetic components. The identification of specific genetic variations that underpin cardiovascular disease is providing new opportunities for diagnostic testing, pharmacogenetics, and drug development. In this review we describe genes that are known to have an important impact on the development of cardiovascular disease and discuss how their identification may improve risk management.


    This review is based on our research and clinical experience in human genetics, pathology, and medicine. Citations for the topics discussed derive from literature searches in PubMed, OMIM (Online McKusick Inheritance in Man), and online US and European patent databases (USPTO and Esp@cenet respectively).

    Genetic influences on blood cholesterol concentrations

    Variations in the genes for low density lipoprotein receptor, apolipoprotein B, and apolipoprotein E have a considerable effect on individuals' plasma cholesterol concentrations (fig 1).

    Fig 1.

    Effects of genetic variation on population distribution of plasma cholesterol concentration. Polymorphisms in the apolipoprotein E gene (APOE) cause an average 10% lowering (E2 allele) or raising (E4 allele) of cholesterol concentration compared with homozygosity for E3. A single defective allele of the apolipoprotein B gene (APOB) has a heterogeneous effect on cholesterol. A defect in the low density lipoprotein receptor gene (LDLR) leads to a rough doubling in cholesterol concentration for heterozygotes and greater increases for homozygotes

    Variations in the low density lipoprotein receptor gene

    Familial hypercholesterolaemia is known to be caused by codominant mutations in the low density lipoprotein (LDL) receptor gene.1 Affected individuals typically have cholesterol concentrations twice the population average for their age and sex. This disorder often results in heart attacks in middle age in the 1 in 500 heterozygotes in populations exposed to a Western diet and in childhood coronary disease in the 1 in a million homozygotes in all populations. The disorder …

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