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Cardiovascular Genetics: A News Round-Up

Summary of Recent Articles of Interest

Wolfgang Lieb, MD and Ramachandran S. Vasan, MD

From the Framingham Heart Study, and Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Framingham, Mass.

Correspondence to Ramachandran S. Vasan, MD, Boston University School of Medicine, Framingham Heart Study, 73 Mount Wayte Ave, Suite 2, Framingham, MA 01702-5803. E-mail vasan@bu.edu

Received April 21, 2009; accepted April 21, 2009.

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Genetic Information Improves Warfarin Dose Estimation Based on Clinical Data

 
1. International Warfarin Pharmacogenetics Consortium; Klein TE, Altman RB, Eriksson N, Gage BF, Kimmel SE, Lee MT, Limdi NA, Page D, Roden DM, Wagner MJ, Caldwell MD, Johnson JA. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. 2009;360:753–764. PMID: 19228618.

Study Hypothesis
Interindividual variation in the response to warfarin therapy is in part determined by genetic factors. Specifically, variation in 2 genes, CYP2C9 (encoding cytochrome P450, family 2, subfamily C, and polypeptide 9) and VKORC1 (encodes vitamin K epoxide reductase complex subunit-1), are known to affect warfarin dose requirements. It is conceivable that an algorithm including genetic predictors in addition to clinical information improves warfarin dose estimation incrementally over algorithms based on clinical data alone.

How Was the Hypothesis Tested?
Within the International Warfarin Pharmacogenetics Consortium, 5052 participants with a target international normalized ratio of 2 to 3 were selected for analyses. Of the eligible patients, 80% (n=4043) were randomly selected as the "derivation cohort," the remaining 20% (n=1009) constituted the "validation cohort." After evaluating different statistical models, a least-squares linear regression model (with the square root of warfarin dose as the dependent variable) best fit the data and was used for further analyses. Three models were compared in their ability to predict the therapeutic warfarin dose (defined as the steady-state dose leading to stable anticoagulation levels): a clinical model (including information about age, height, weight, race, enzyme inducer status, and Amiodarone use status), a fixed-dose model (5 mg per day), and a pharmacogenetic model that included CYP2C9 and VKORC1 genotypic . . . [Full Text of this Article]