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Association analysis of GRK3 gene promoter variants in cocaine abuse

Guindalini, Camilaa c; Collier, Davida b; Laranjeira, Ronaldod; Barrett, Tom B.e f; Kelsoe, Johne f; Castelo, Adautod; Vallada, Homerob c; Breen, Geromea b

doi: 10.1097/YPG.0b013e3280ae6c3d
Brief Report

The G protein-coupled receptor kinase 3 gene (GRK3) is a candidate gene for cocaine adiction because it is involved in the regulation of several neurotransmitter receptors, including the response to dopaminergic agonists such as methamphetamine and cocaine. We hypothesized that genetic variants in the GRK3 gene might be associated with an increased risk of cocaine addiction. To test this, we genotyped three variants located in 5′ untranslated and promoter regions of the gene in a sample of 711 cocaine users and 862 healthy control individuals from Sao Paulo, Brazil. Genotypic, allelic and haplotypic analyses provided no evidence for an association between alleles at these polymorphisms and cocaine abuse in this sample. Population stratification was tested for and its effect corrected for, but this did not affect the association test results. In conclusion, our results do not support a major role for GRK3 gene promoter variants in cocaine addiction.

aMRC Social Genetic and Developmental Psychiatry Research Centre

bDivision of Psychological Medicine, Institute of Psychiatry, King's College London, UK

cDepartment of Psychiatry, University of São Paulo Medical School

dUNIAD (Unit of Drug and Alcohol Research), Department of Psychiatry, Federal University of São Paulo, Brazil

eDepartment of Psychiatry, University of California San Diego, San Diego

fDepartment of Psychiatry, San Diego VA Healthcare System, La Jolla, California, USA

Correspondence to Gerome Breen, Section of Genetics, Room 222 SGDP Centre, PO 81, MRC Social Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, Kings College London SE5 8AF, UK

Tel: +44 20 7848 0409; fax: +44 20 7848 0575;

e-mail: g.breen@iop.kcl.ac.uk

Received 10 September 2006 Accepted 7 December 2006

© 2007 Lippincott Williams & Wilkins, Inc.