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Sequencing drug response with HapMap

The Pharmacogenomics Journal volume 5, pages 149–156 (2005)Cite this article

Abstract

The information about how DNA sequence varies across the human genome is crucial for unravelling the genetic basis of drug response. A haplotype map, or HapMap, intended to reveal such a variation pattern, has been recently developed by the International HapMap Consortium. Here, we present a conceptual model for directly characterizing specific DNA sequence variants that are responsible for drug response based on the haplotype structure provided by HapMap. Our model is developed in the maximum likelihood context, incorporated by clinically meaningful mathematical functions that model drug response and implemented with the EM algorithm. Our model is employed to a pharmacogenetic study of cardiovascular disease with 107 patients. We found that the haplotype constituted by allele Gly16 (G) at codon 16 and allele Glu27 (G) at codon 27 genotyped within the β2AR candidate gene exhibits a different effect on heart rate curve from the rest haplotypes. Parents with the diplotype consisting of two copies of haplotype GG are more sensitive in heart rate to increasing dosages of dobutamine than those with other haplotypes. This model provides a powerful tool for elucidating the genetic variants of drug response and ultimately designing personalized medications based on each patient's genetic constitution.

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Acknowledgements

This work is supported by an Outstanding Young Investigator Award of the National Natural Science Foundation of China (30128017), a University of Florida Research Opportunity Fund (02050259) and a University of South Florida Biodefense grant (7222061-12) to R W. The publication of this manuscript was approved as Journal Series No. R-10575 by the Florida Agricultural Experiment Station.

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Authors and Affiliations

  1. Department of Statistics, University of Florida, Gainesville, FL, USA

    M Lin & R Wu

  2. Department of Pharmacy Practice, University of Florida, Gainesville, FL, USA

    C Aquilante & J A Johnson

Authors
  1. M Lin
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  2. C Aquilante
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  3. J A Johnson
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  4. R Wu
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Correspondence to R Wu.

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Lin, M., Aquilante, C., Johnson, J. et al. Sequencing drug response with HapMap. Pharmacogenomics J 5, 149–156 (2005). https://doi.org/10.1038/sj.tpj.6500302

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