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Genetic and Environmental Sources of Variation in Heart Rate Response to Infused Nicotine in Twins

¹ Center for Health Sciences, SRI International, Menlo Park, California; ² Department of Genetics, University of North Carolina, Raleigh, North Carolina; and ³ Division of Clinical Pharmacology, Departments of Medicine, Psychiatry and Biopharmaceutical Sciences, University of California, San Francisco, California

Requests for reprints: Gary E. Swan, Center for Health Sciences, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025. Phone: 650-859-5322; Fax: 650-859-5099. E-mail: gary.swan{at}sri.com

The heart rate response to nicotine may be an important component of the process leading to dependence. The present study is the first to determine the extent to which genetic and environmental sources play a role in various components of the heart rate response. One hundred and ten monozygotic and 29 dizygotic twin pairs received an i.v. infusion of nicotine and cotinine over 30 min. Before, during, and for 30 min after infusion, heart rate was measured via an electronic monitor. The clearance of nicotine was determined as a measure of the rate of nicotine metabolism. Average resting heart rate before infusion was 64.7 beats per minutes (bpm), and at the termination of infusion, heart rate had increased to an average of 72.7 bpm. At 30 min after infusion, heart rate had decreased to 67.5 bpm. Age, current smoking status, body mass index, and nicotine clearance were associated significantly with heart rate levels over the full 60 min of measurement. After adjustment for several covariates, including dose of administered nicotine and rate of nicotine clearance, the variance in several characteristics of the heart rate response curve was examined for the relative contribution from genetic and environmental sources. In the total sample, as much as 30.3% of the variance in the acceleration of heart rate was due to additive genetic sources. In nonsmokers, 34.8% and 31.0% of variance in the acceleration and deceleration of heart rate, respectively, was due to genetic sources. Heart rate acceleration and deceleration may be a reflection of central nervous system responsiveness to nicotine. The contribution from genetic sources to heart rate response characteristics should be investigated further as a potential endophenotype for use in genetic studies of nicotine dependence. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1057–64)