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Monday, February 26, 2007

Diplotypes of the Human Serotonin 1B Receptor Promoter Predict Growth Hormone Responses to Sumatriptan in Abstinent Alcohol-Dependent Men


Biological Psychiatry
Article in Press, Corrected Proof Available on-line 9 January 2007


Howard B. Mossa, E-mail: mossh@mail.nih.gov

Thomas L. Hardiec,

John P. Dahlb,

Wade Berrettinib and

Ke Xud

aCenter for the Studies of Addiction
bCenter for Neurobiology and Behavior (JPD, WB), University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
cDepartment of Nursing (TLH), University of Delaware, Newark, Delaware
dNational Institute on Alcohol Abuse and Alcoholism (KX), Bethesda, Maryland

Received 27 October 2005; revised 23 June 2006; accepted 15 August 2006. Available online 9 January 2007.


Background

Some studies have associated alcohol dependence (AD) with the human serotonin (5-HT)1B receptor (HTR1B). This investigation explored the functional responsivity of HTR1B in abstinent AD men using a sumatriptan challenge, while measuring genetic heterogeneity in the HTR1B promoter.

Methods

Abstinent AD men (n = 27) and abstinent men without any alcohol use disorder (n = 19) were administered 6 mg of sumatriptan succinate, subcutaneously. Plasma samples collected over the following 2 hours were assayed for growth hormone (GH) concentrations. His DNA was genotyped for the A-161T and T-261G polymorphisms of the HTR1B promoter and diplotypes determined.

Results

Integrated GH responses were predicted by interactions of AD and promoter diplotypes, as well as subject ethnicity. The final model accounted for nearly 35% of the variance in GH responses. Post hoc evaluation revealed that AD was associated with a blunting of GH secretion only among individuals with the most common HTR1B diplotype (TT/TT).

Conclusions

A blunting of GH responses in abstinent AD men was observed only among those with the most common HTR1B promoter diplotype. Less common promoter diplotypes appeared protective. Controlling for genetic background is a useful augmentation of case-control pharmacological challenge strategies designed to elucidate the psychobiology of AD and other complex disorders.


Corresponding Author Contact InformationAddress reprint requests to Howard B. Moss, M.D., Associate Director for Education and Career Development, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, #3097, Bethesda, MD 20892-9304
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