Asset Details
Do you wish to reserve the book?
A CHRNA5 Smoking Risk Variant Decreases the Aversive Effects of Nicotine in Humans
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
A CHRNA5 Smoking Risk Variant Decreases the Aversive Effects of Nicotine in Humans
Do you wish to request the book?
A CHRNA5 Smoking Risk Variant Decreases the Aversive Effects of Nicotine in Humans
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
A CHRNA5 Smoking Risk Variant Decreases the Aversive Effects of Nicotine in Humans
2015
Overview
Genome-wide association studies have implicated the CHRNA5-CHRNA3-CHRNB4 gene cluster in risk for heavy smoking and several smoking-related disorders. The heavy smoking risk allele might reduce the aversive effects of nicotine, but this hypothesis has not been tested in humans. We evaluated the effects of a candidate causal variant in CHRNA5, rs16969968, on the acute response to nicotine in European American (EA) and African American (AA) smokers (n=192; 50% AA; 73% male). Following overnight abstinence from nicotine, participants completed a protocol that included an intravenous (IV) dose of saline and two escalating IV doses of nicotine. The outcomes evaluated were the aversive, pleasurable, and stimulatory ratings of nicotine's effects, cardiovascular reactivity to nicotine, withdrawal severity, and cognitive performance before and after the nicotine administration session. The heavy smoking risk allele (rs16969968*A; frequency=28% (EA) and 6% (AA)) was associated with lower ratings of aversive effects (P<5 × 10(-8)) with marked specificity. This effect was evident in EA and AA subjects analyzed as separate groups and was most robust at the highest nicotine dose. Rs16969968*A was also associated with greater improvement on a measure of cognitive control (Stroop Task) following nicotine administration. These findings support differential aversive response to nicotine as one likely mechanism for the association of CHRNA5-CHRNA3-CHRNB4 with heavy smoking.
Publisher
Nature Publishing Group
Subject
/ Blood Pressure - drug effects
/ Cognition Disorders - chemically induced
/ Cognition Disorders - etiology
/ Cotinine - analogs & derivatives
/ Female
/ Genetics
/ Genome-Wide Association Study
/ Humans
/ Male
/ Medicine
/ Nerve Tissue Proteins - genetics
/ Nicotine
/ Nicotinic Agonists - adverse effects
/ Original
/ Polymorphism, Single Nucleotide - genetics
/ Receptors, Nicotinic - genetics
/ Smoking
/ Substance Withdrawal Syndrome - blood
/ Substance Withdrawal Syndrome - physiopathology
