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Pharmacogenetics of stimulant abuse liability: association of CDH13 variant with amphetamine response in a racially-heterogeneous sample of healthy young adults

Abstract

Rationale

A previous genome-wide association study (GWAS) in a predominately Caucasian sample of healthy young adults linked greater amphetamine-induced rewarding effects with the rs3784943 G allele of the cadherin 13 (CDH13; i.e., a cell adhesion molecule implicated in neuronal connectivity) gene. This association has not been subsequently examined, nor has it been studied in Asian populations, which may have greater frequencies of the risk allele.

Objective

The objective of this study was to examine the association of rs3784943 with amphetamine response in a racially heterogeneous sample (37 % Asian) of healthy young adults.

Methods

Participants (N = 84; 18–35 years old) genotyped for rs3784943 completed counterbalanced sessions involving 20 mg oral d-amphetamine or placebo administration. At both sessions, cardiovascular and subjective drug effects measures were collected.

Results

In the combined racially heterogeneous sample, amphetamine (vs. placebo) effects were significantly greater on “Feel Drug” ratings (p < 0.05) and marginally greater on “Feel High” ratings and systolic blood pressure (p < 0.10) in G/A + G/G genotypes than A/A genotypes. The G allele was more common among Asian than other racial groups. Among the subsample of Asian participants (N = 31), drug effects were significantly greater on Feel Drug (p < 0.05) and marginally greater on Feel High and heart rate (p < 0.10) among Asians with G/A + G/G (vs. A/A) genotypes.

Conclusions

In concert with a previous GWAS result, this candidate gene study provides convergent evidence implicating CDH13 rs3784943 variant in d-amphetamine’s drug effect profile and suggests generalization to Asian populations. CDH13 and genes coding for other cell adhesion molecules may be worthy of study in the biology of psychostimulant abuse liability.

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Acknowledgments

This research was supported by the National Institute on Drug Abuse K08-DA025041 (Leventhal PI). The contents do not represent the views of the US Department of Veterans Affairs or the US government.

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Correspondence to Adam M. Leventhal.

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The study was reviewed and approved by the Institutional Review Board at the University of Southern California in accordance with the Code of Federal Regulations (Title 45, Part 46) adopted by the National Institutes of Health and the Office for Protection from Research Risks of the US Federal Government and was conducted ethically in accordance with the Helsinki Declaration of 1964 (revised 1989) and the National Advisory Council on Drug Abuse Recommended Guidelines for the Administration of Drugs to Human Subjects.

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The authors declare that they have no conflict of interest.

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Leventhal, A.M., Kirkpatrick, M.G., Pester, M.S. et al. Pharmacogenetics of stimulant abuse liability: association of CDH13 variant with amphetamine response in a racially-heterogeneous sample of healthy young adults. Psychopharmacology 234, 307–315 (2017). https://doi.org/10.1007/s00213-016-4462-z

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  • DOI: https://doi.org/10.1007/s00213-016-4462-z

Keywords

  • Amphetamine
  • Genetics
  • Cell adhesion molecules
  • Drug reward
  • Race