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The Leu72Met Polymorphism of the Prepro-ghrelin Gene is Associated With Alcohol Consumption and Subjective Responses to Alcohol: Preliminary Findings

Artikel i vetenskaplig tidskrift
Författare Petra Suchankova
J. Yan
M. L. Schwandt
B. L. Stangl
Elisabeth Jerlhag
Jörgen Engel
C. A. Hodgkinson
V. A. Ramchandani
L. Leggio
Publicerad i Alcohol and Alcoholism
Volym 52
Nummer/häfte 4
Sidor 425-430
ISSN 0735-0414
Publiceringsår 2017
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi
Sidor 425-430
Språk en
Länkar doi.org/10.1093/alcalc/agx021
Ämnesord receptor gene, drinking, individuals, dependence, system, reward, Substance Abuse
Ämneskategorier Klinisk medicin

Sammanfattning

The orexigenic peptide ghrelin may enhance the incentive value of food-, drug- and alcohol-related rewards. Consistent with preclinical findings, human studies indicate a role of ghrelin in alcohol use disorders (AUD). In the present study an a priori hypothesis-driven analysis was conducted to investigate whether a Leu72Met missense polymorphism (rs696217) in the prepro-ghrelin gene (GHRL), is associated with AUD, alcohol consumption and subjective responses to alcohol. Association analysis was performed using the National Institute on Alcohol Abuse and Alcoholism (NIAAA) clinical sample, comprising AUD individuals and controls (N = 1127). Then, a post-hoc analysis using data from a human laboratory study of intravenous alcohol self-administration (IV-ASA, N = 144) was performed to investigate the association of this SNP with subjective responses following a fixed dose of alcohol (priming phase) and alcohol self-administration (ad libitum phase). The case-control study revealed a trend association (N = 1127, OR = 0.665, CI = 0.44-1.01, P = 0.056) between AUD diagnosis and Leu72Met. In AUD subjects, the SNP was associated with significantly lower average drinks per day (n = 567, beta = -2.49, 95% CI = -4.34 to -0.64, P = 0.008) and significantly fewer heavy drinking days (n = 567, beta = -12.00, 95% CI = -19.10 to -4.89, P < 0.001). The IV-ASA study further revealed that 72Met carriers had greater subjective responses to alcohol (P < 0.05) when compared to Leu72Leu both at priming and during ad lib self-administration. Although preliminary, these findings suggest that the Leu72Leu genotype may lead to increased risk of AUD possibly via mechanisms involving a lower response to alcohol resulting in excessive alcohol consumption. Further investigations are warranted. We investigated whether a Leu72Met missense polymorphism in the prepro-ghrelin gene, is associated with alcohol use disorder, alcohol consumption and subjective responses to alcohol. Although preliminary, results suggest that the Leu72Leu genotype may lead to increased risk of alcohol use disorder possibly via mechanisms involving a lower response to alcohol.

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