1. ¹The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA
2. ²Karolinska Institute, Stockholm, Sweden
3. ³The Laboratory of Statistical Genetics, The Rockefeller University, New York, NY, USA
4. ⁴Laboratory of Clinical Science, NIAAA, NIH, Bethesda MD, USA

Correspondence: Dr G Bart, The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. Tel: +212 327 8282; Fax: +212 327 7023; E-mail: bartg@rockefeller.edu

Received 28 June 2004; Revised 24 August 2004; Accepted 22 September 2004; Published online 3 November 2004.

Abstract

The -opioid receptor (MOR), through its effects on reward and stress-responsivity, modulates alcohol intake in both animal and human laboratory studies. We have previously demonstrated that the frequently occurring A118G single-nucleotide polymorphism (SNP) in exon 1 of the MORgene (OPRM1), which encodes an amino-acid substitution, is functional and receptors encoded by the variant 118G allele bind the endogenous opioid peptide -endorphin with three-fold greater affinity than prototype receptors. Other groups subsequently reported that this variant alters stress-responsivity in normal volunteers and also increases the therapeutic response to naltrexone (a -preferring opioid antagonist) in the treatment of alcohol dependence. We compared frequencies of genotypes containing an 118G allele in 389 alcohol-dependent individuals and 170 population-based controls without drug or alcohol abuse or dependence. The A118G SNP was present in the Hardy–Weinberg equilibrium with an overall frequency of the 118G allele of 10.9%. There was a significant overall association between genotypes with an 118G allele and alcohol dependence (p=0.0074). The attributable risk for alcohol dependence in subjects with an 118G allele was 11.1%. There was no difference in A118G genotype between type 1 and type 2 alcoholics. In central Sweden, the functional variant 118G allele in exon 1 of OPRM1 is associated with an increased attributable risk for alcohol dependence.