Abstract
Aims: The molecular epidemiological studies on the association of the opioid receptor µ-1 (OPRM1) polymorphism A118G (Asn40Asp, rs1799971) and alcohol use disorders have given conflicting results. The aim of this study was to test the possible association of A118G polymorphism and alcohol use disorders and alcohol consumption in three large cohort-based study samples. Methods: The association between the OPRM1 A118G (Asn40Asp, rs1799971) polymorphism and alcohol use disorders and alcohol consumption was analyzed using three different population-based samples: (a) a Finnish cohort study, Health 2000, with 503 participants having a DSM-IV diagnosis for alcohol dependence and/or alcohol abuse and 506 age- and sex-matched controls; (b) a Finnish cohort study, FINRISK (n = 2360) and (c) the Helsinki Birth Cohort Study (n = 1384). The latter two populations lacked diagnosis-based phenotypes, but included detailed information on alcohol consumption. Results: We found no statistically significant differences in genotypic or allelic distribution between controls and subjects with alcohol dependence or abuse diagnoses. Likewise no significant effects were observed between the A118G genotype and alcohol consumption. Conclusion: These results suggest that A118G (Asn40Asp) polymorphism may not have a major effect on the development of alcohol use disorders at least in the Finnish population.
Highlights
Alcohol dependence and alcohol abuse are complex disorders involving multiple genetic and environmental factors
Alcohol dependence and alcohol abuse as well as mood and anxiety disorders were assessed by using a diagnostic mental health interview, Munich-Composite International Diagnostic Interview (M-CIDI), yielding the diagnosis based on DSM-IV criteria (Diagnostic and Statistical Manual of Mental Disorders, 4th edn, American Psychiatric Association 2000)
The association between OPRM1 A118G (Asn40Asp, rs1799971) polymorphism and alcohol use disorders was analyzed in a population-based sample consisting of genotyping results from 503 individuals with a DSM-IV-based diagnosis of alcohol dependence or alcohol abuse and their 506 age- and sex-matched controls
Summary
Alcohol dependence and alcohol abuse are complex disorders involving multiple genetic and environmental factors. The binding of β-endorphin to μ-opioid receptors may reinforce alcohol drinking directly or indirectly through increased dopamine levels in the brain reward areas (Gianoulakis, 2009). Genetic variation in the μ-opioid receptor may affect the risk of developing alcohol use disorder by affecting the individual’s response to alcohol. This hypothesis is supported by animal studies: e.g. mice lacking the μ-opioid receptor self-administer less alcohol than wild type mice (Roberts et al, 2000; Hall et al, 2001). Taken together, accumulating evidence implicates human μ-opioid receptor as an important determinant in the reinforcing effects of alcohol, making it a good candidate gene in the search of the genetic variation influencing the development of alcohol use disorders
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