FKBP5 variation is associated with the acute and chronic effects of nicotine

Title:
FKBP5 variation is associated with the acute and chronic effects of nicotine
Authors:
Jensen, K. P.; Herman, A. I.; Morean, Meghan E. ( 0000-0003-4865-1155 ) ; Kranzler, H. R.; Gelernter, J.; Sofuoglu, Mehmet
Abstract:
Stress and hormones released in response to stress influence the effects of nicotine and the severity of nicotine withdrawal. Here, we systematically examine the contribution of a stress response gene, FKBP5, to the acute and chronic behavioral effects of nicotine in smokers. Subjects were European- and African-American (EA and AA) heavy smokers who participated in an intravenous (IV) nicotine administration study (total n=169). FKBP5 rs3800373 genotype was analyzed for association to several outcomes, including nicotine withdrawal and the acute subjective, heart rate (HR), blood pressure and plasma cortisol responses to IV nicotine. Nicotine withdrawal was also examined in relation to rs3800373 allele frequencies in an independent cohort of EA and AA current smokers (n=3821). For a subset of laboratory subjects FKBP5 mRNA (n=48) expression was explored for an association to the same outcomes. The rs3800373 minor allele was associated with less severe nicotine withdrawal in laboratory subjects and the independent cohort of smokers. The rs3800373 minor allele was also associated with lower subjective ratings of negative drug effects in response to IV nicotine. Low FKBP5 mRNA expression was associated lower cortisol levels, lower subjective ratings of negative drug effects and a blunted HR response to nicotine. Stress hormone regulation via FKBP5 warrants further investigation as a potential contributor to the effects of nicotine withdrawal, which occurs commonly, and has an important role in the maintenance of smoking behavior and relapse following a quit attempt.
Citation:
Jensen, K.P., A.I. Herman, M.E. Morean, et al. 2015. "FKBP5 variation is associated with the acute and chronic effects of nicotine." Pharmacogenomics Journal 15(4): 340-346.
Publisher:
Nature Publishing Group
DATE ISSUED:
2015-08
Department:
Psychology
Type:
Article
PUBLISHED VERSION:
10.1038/tpj.2014.76
Additional Links:
http://www.nature.com/doifinder/10.1038/tpj.2014.76
PERMANENT LINK:
http://hdl.handle.net/11282/613539

Full metadata record

DC FieldValue Language
dc.contributor.authorJensen, K. P.en
dc.contributor.authorHerman, A. I.en
dc.contributor.authorMorean, Meghan E.en
dc.contributor.authorKranzler, H. R.en
dc.contributor.authorGelernter, J.en
dc.contributor.authorSofuoglu, Mehmeten
dc.date.accessioned2016-06-17T12:19:22Zen
dc.date.available2016-06-17T12:19:22Zen
dc.date.issued2015-08en
dc.identifier.citationJensen, K.P., A.I. Herman, M.E. Morean, et al. 2015. "FKBP5 variation is associated with the acute and chronic effects of nicotine." Pharmacogenomics Journal 15(4): 340-346.en
dc.identifier.issn1470-269Xen
dc.identifier.urihttp://hdl.handle.net/11282/613539en
dc.description.abstractStress and hormones released in response to stress influence the effects of nicotine and the severity of nicotine withdrawal. Here, we systematically examine the contribution of a stress response gene, FKBP5, to the acute and chronic behavioral effects of nicotine in smokers. Subjects were European- and African-American (EA and AA) heavy smokers who participated in an intravenous (IV) nicotine administration study (total n=169). FKBP5 rs3800373 genotype was analyzed for association to several outcomes, including nicotine withdrawal and the acute subjective, heart rate (HR), blood pressure and plasma cortisol responses to IV nicotine. Nicotine withdrawal was also examined in relation to rs3800373 allele frequencies in an independent cohort of EA and AA current smokers (n=3821). For a subset of laboratory subjects FKBP5 mRNA (n=48) expression was explored for an association to the same outcomes. The rs3800373 minor allele was associated with less severe nicotine withdrawal in laboratory subjects and the independent cohort of smokers. The rs3800373 minor allele was also associated with lower subjective ratings of negative drug effects in response to IV nicotine. Low FKBP5 mRNA expression was associated lower cortisol levels, lower subjective ratings of negative drug effects and a blunted HR response to nicotine. Stress hormone regulation via FKBP5 warrants further investigation as a potential contributor to the effects of nicotine withdrawal, which occurs commonly, and has an important role in the maintenance of smoking behavior and relapse following a quit attempt.en
dc.language.isoen_USen
dc.publisherNature Publishing Groupen
dc.identifier.doi10.1038/tpj.2014.76en
dc.relation.urlhttp://www.nature.com/doifinder/10.1038/tpj.2014.76en
dc.subject.departmentPsychologyen_US
dc.titleFKBP5 variation is associated with the acute and chronic effects of nicotineen_US
dc.typeArticleen
dc.identifier.journalThe Pharmacogenomics Journalen
dc.subject.keywordNicotineen_US
dc.subject.keywordCarrier proteinsen_US
dc.subject.keywordStress (Psychology)en_US
dc.subject.keywordHormonesen_US
dc.subject.keywordCigarette smokersen_US
dc.identifier.volume15en_US
dc.identifier.issue4en_US
dc.identifier.startpage340en_US
dc.rightsArchived with thanks to The Pharmacogenomics Journalen
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