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Association of CamK2A genetic variants with transition time from occasional to regular heroin use in a sample of heroin-dependent individuals

Eirich, Antoniaa; Biermann, Teresaa; Müller, Christian P.a; Kornhuber, Johannesa; Benyamin, Bebenb,c; Hulse, Gary K.d,e; Wildenauer, Dieter B.d; Schwab, Sibylle G.a,f,g

doi: 10.1097/YPG.0000000000000208

Objectives Susceptibility to heroin dependence is strongly influenced by genetic factors with heritability estimates as high as 0.7. A number of genes, as well as environmental factors, are likely to contribute to its etiology. Not all individuals who have ever tried heroin at some stage during their lifetime become dependent on heroin. It has been suggested that genetic factors might be more important in the transition stage to heroin dependence rather than in environmental exposures and experimenting with heroin. As the features of substance dependence and memory formation have been found to be strikingly similar, we have focused on a key enzyme involved in long-term potentiation and synaptic plasticity, namely the calcium-dependent/calmodulin-dependent protein kinase IIα (CAMKIIa). We hypothesized, that CamK2A genetic variation may play a role in the transition from occasional to regular heroin use.

Materials and methods Using quantitative trait association analysis, we addressed this hypothesis by correlating the self-reported time interval between occasional and regular heroin use with the frequency of 12 single nucleotide polymorphisms located within the genomic region of the CamK2A gene. A sample of 570 Caucasian patients was available for analysis.

Results Single marker association analysis (rs10066581, P=0.007), as well as haplotype analysis (global P=0.005), suggested an association with the quantitative trait ‘time interval from occasional to regular heroin use.’

Conclusion Our results propose that genetic variants located in the genomic region of the CamK2A gene may be involved in transition time from occasional to regular heroin use.

aDepartment of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

bSchool of Health Sciences, Australian Centre for Precision Health, University of South Australia Cancer Research Institute, University of South Australia, Adelaide, South Australia

cInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland

dDivision of Psychiatry, University of Western Australia

eSchool of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia

fFaculty of Science, Medicine and Health, International Unit, University of Wollongong

gIllawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia

Antonia Eirich: The present work was performed in (partial) fulfilment of the requirements for obtaining the degree ''.

Correspondence to Sibylle G. Schwab, PhD, Faculty of Science, Medicine and Health, International Unit, University of Wollongong, Northfields Avenue, Wollongong, NSW 2522, Australia Tel: +61 242 215 816; fax: +61 242 213 151; e-mail:

Received February 22, 2018

Received in revised form August 14, 2018

Accepted September 5, 2018

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