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Genetic association studies: personalized medicine in cardiac transplantation

Nature Clinical Practice Cardiovascular Medicine volume 3, pages 58–59 (2006)Cite this article

Two great achievements of the 20th century were organ transplantation and completion of the first draft of the human genome. Since the introduction of effective pharmacologic immunosuppression, cardiac transplantation has revolutionized the treatment of end-stage heart failure, allowing the majority of patients to return to fully active lives. Long-term survival after transplantation, however, varies extensively between patients, and depends on patient-related, donor-related and as yet unknown factors. Cardiac transplantation research has focused largely on predicting risk and determining pathogenic pathways, and hence finding targets for intervention. The idea that genotyping could provide this information is therefore very attractive. The Human Genome Project is now ready to provide the information and technology required for personalized treatment. This viewpoint will discuss genetic association studies, their potential application to personalized medicine at different stages before and after cardiac transplantation, and the complexities involved.

Single-nucleotide polymorphisms (SNPs) are the most common known variation in the human genome. SNPs alter the nucleotide sequence in an otherwise conserved region of DNA and are found roughly every 12,000 base pairs. Importantly, base changes in both protein-coding and noncoding regions of DNA can significantly affect the chance of disease.1 Only 2% of the human genome is transcribed into messenger RNA, and hence protein, and these regions have received particular attention in the search for functionally significant SNPs; however, it is believed that as much as 40% of the genome is transcribed into RNA, making it important to recognize the potential functional effects of nonexonic SNPs. This 'extra' RNA might play a role in regulating the genome through direct effects on expression.2

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Authors and Affiliations

  1. post-doctoral clinician scientist,

    Anne B Taegtmeyer, Paul JR Barton & Magdi H Yacoub

  2. Molecular Biology and Assistant Director of Research of the Magdi Yacoub Institute,

    Anne B Taegtmeyer, Paul JR Barton & Magdi H Yacoub

  3. Professor of Cardiothoracic Surgery and Director of Research, at the Heart Science Centre, Imperial College London, Harefield, Middlesex, UK

    Anne B Taegtmeyer, Paul JR Barton & Magdi H Yacoub

Authors
  1. Anne B Taegtmeyer
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  2. Paul JR Barton
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  3. Magdi H Yacoub
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Correspondence to Anne B Taegtmeyer.

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The authors declare no competing financial interests.

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Taegtmeyer, A., Barton, P. & Yacoub, M. Genetic association studies: personalized medicine in cardiac transplantation. Nat Rev Cardiol 3, 58–59 (2006). https://doi.org/10.1038/ncpcardio0453

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