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Variation in the gene coding for the M5 muscarinic receptor (CHRM5) influences cigarette dose but is not associated with dependence to drugs of addiction : evidence from a prospective population based cohort study of young adults

Anney, Richard J. L., Lotfi-Miri, Mehrnoush, Olsson, Craig A., Reid, Sophie C., Hemphill, Sheryl A. and Patton, George C. 2007, Variation in the gene coding for the M5 muscarinic receptor (CHRM5) influences cigarette dose but is not associated with dependence to drugs of addiction : evidence from a prospective population based cohort study of young adults, BMC genetics, vol. 8, no. 46, pp. 1-9, doi: 10.1186/1471-2156-8-46.

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Title Variation in the gene coding for the M5 muscarinic receptor (CHRM5) influences cigarette dose but is not associated with dependence to drugs of addiction : evidence from a prospective population based cohort study of young adults
Author(s) Anney, Richard J. L.
Lotfi-Miri, Mehrnoush
Olsson, Craig A.ORCID iD for Olsson, Craig A. orcid.org/0000-0002-5927-2014
Reid, Sophie C.
Hemphill, Sheryl A.
Patton, George C.
Journal name BMC genetics
Volume number 8
Issue number 46
Start page 1
End page 9
Total pages 9
Publisher BioMed Central
Place of publication London, England
Publication date 2007-07-03
ISSN 1471-2156
Keyword(s) drug addiction
Summary Background: The mesolimbic structures of the brain are important in the anticipation and perception of reward. Moreover, many drugs of addiction elicit their response in these structures. The M5 muscarinic receptor (M5R) is expressed in dopamine-containing neurones of the substantia nigra pars compacta and ventral tegmental area, and regulates the release of mesolimbic dopamine. Mice lacking M5R show a substantial reduction in both reward and withdrawal responses to morphine and cocaine. The CHRM5, the gene that codes for the M5R, is a strong biological candidate for a role in human addiction. We screened the coding and core promoter sequences of CHRM5 using denaturing high performance liquid chromatography to identify common polymorphisms. Additional polymorphisms within the coding and core promoter regions that were identified through dbSNP were validated in the test population. We investigated whether these polymorphisms influence substance dependence and dose in a cohort of 1947 young Australians.

Results: Analysis was performed on 815 participants of European ancestry who were interviewed at wave 8 of the cohort study and provided DNA. We observed a 26.8% increase in cigarette consumption in carriers of the rs7162140 T-allele, equating to 20.1 cigarettes per week (p=0.01). Carriers of the rs7162140 T-allele were also found to have nearly a 3-fold increased risk of developing cannabis dependence (OR=2.9 (95%CI 1.1-7.4); p=0.03).

Conclusion: Our data suggest that variation within the CHRM5 locus may play an important role in tobacco and cannabis but not alcohol addiction in European ancestry populations. This is the first study to show an association between CHRM5 and substance use in humans. These data support the further investigation of this gene as a risk factor in substance use and dependence.
Notes This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Language eng
DOI 10.1186/1471-2156-8-46
Field of Research 179999 Psychology and Cognitive Sciences not elsewhere classified
Socio Economic Objective 970117 Expanding Knowledge in Psychology and Cognitive Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2007, Anney et al.
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30041298

Document type: Journal Article
Collections: Faculty of Health
School of Psychology
Open Access Collection
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