The mu opioid receptor is implicated in the reward, tolerance and withdrawal effects of alcohol and other drugs of abuse. We directly sequenced the human mu opioid receptor locus, OPRM1, to detect natural variation that might affect the function of this receptor or be associated with psychiatric phenotypes related to opioid function. Four DNA sequence variants were found: three amino acid substitutions (Ala6Val [rare], Asn40Asp [frequency 10%], Ser147Cys [rare]) and one intronic variant (IVS2+691G/C [frequency 50%]). OPRM1 alleles, genotypes and haplotypes from three psychiatrically characterized population samples (N = 791) were used to perform association and sib-pair linkage analyses to alcohol dependence. There was no significant association or linkage between OPRM1 and alcohol dependence in any of the three population samples. These results and power calculations strongly suggest that variation at the mu opioid receptor is not involved in vulnerability to DSM-III-R Alcohol Dependence. Variation at this gene could be investigated for possible association to response to opiate pharmacotherapy and to variation in opioid function, that is, pain or nociception and the regulation of hypothalamic-pituitary function.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Intramural Research (Z01)
Project #
1Z01AA000298-02
Application #
6097602
Study Section
Special Emphasis Panel (LNG)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
National Institute on Alcohol Abuse and Alcoholism
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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