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Genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking

Artikel i vetenskaplig tidskrift
Författare Petra Suchankova
Staffan Nilsson
Bettina von der Pahlen
Pekka Santtila
Kenneth Sandnabba
Ada Johansson
Patrick Jern
Jörgen Engel
Elisabeth Jerlhag
Publicerad i Addiction Biology
Volym 21
Nummer/häfte 2
Sidor 481–488
ISSN 1355-6215
Publiceringsår 2016
Publicerad vid Institutionen för matematiska vetenskaper, matematisk statistik
Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi
Sidor 481–488
Språk en
Länkar dx.doi.org/10.1111/adb.12277
Ämnesord Candidate gene association study;gastrointestinal hormones;substance use disorder
Ämneskategorier Molekylär medicin (genetik och patologi)

Sammanfattning

The multifaceted gut-brain peptide ghrelin and its receptor (GHSR-1a) are implicated in mechanisms regulating not only the energy balance but also the reward circuitry. In our pre-clinical models, we have shown that ghrelin increases whereas GHSR-1a antagonists decrease alcohol consumption and the motivation to consume alcohol in rodents. Moreover, ghrelin signaling is required for the rewarding properties of addictive drugs including alcohol and nicotine in rodents. Given the hereditary component underlying addictive behaviors and disorders, we sought to investigate whether single nucleotide polymorphisms (SNPs) located in the pre-proghrelin gene (GHRL) and GHSR-1a gene (GHSR) are associated with alcohol use, measured by the alcohol use disorders identification test (AUDIT) and smoking. Two SNPs located in GHRL, rs4684677 (Gln90Leu) and rs696217 (Leu72Met), and one in GHSR, rs2948694, were genotyped in a subset (n = 4161) of a Finnish population-based cohort, the Genetics of Sexuality and Aggression project. The effect of these SNPs on AUDIT scores and smoking was investigated using linear and logistic regressions, respectively. We found that the minor allele of the rs2948694 SNP was nominally associated with higher AUDIT scores (P = 0.0204, recessive model) and smoking (P = 0.0002, dominant model). Furthermore, post hoc analyses showed that this risk allele was also associated with increased likelihood of having high level of alcohol problems as determined by AUDIT scores ≥ 16 (P = 0.0043, recessive model). These convergent findings lend further support for the hypothesized involvement of ghrelin signaling in addictive disorders.

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