ABSTRACT
Title
Involvement of the mu-opioid receptor gene polymorphism A118G in alcohol dependent patients.
Authors
V. Marini, C. Fucile, ML. Zuccoli, D. Barciocco, L. Robbiano, F. Mattioli, A. Martelli.
Dept. of Internal Medicine (Di.M.I.) - Clinical pharmacology and toxicology Unit. University of Genoa, Italy.
Dept. of Internal Medicine (Di.M.I.) - Clinical pharmacology and toxicology Unit. University of Genoa, Italy.
Abstract
The endogenous opioid system has been implicated in the development of alcohol dependence due to its prominent role in the central rewarding mechanism (Di Chiara et al, 1996).
A common single nucleotide polymorphism A118G in the mu-opioid receptor gene (OPRM1) has been suggested to contribute to individual variability in alcohol addiction (Ray La et al, 2004). This transition (A→G), leading to an aminoacid substitution (Asn40 to Asp 40) in a highly conserved N-glycosylation site, can cause a significant change in mu-receptor function (Bond et al, 1998; Zhang et al, 2005). Several studies have been conducted in order to identify an association of the A118G with alcohol abuse however they have not provided any unified finding (Mague et al, 2010).
The aim of this study is to investigate the involvement of A118G in alcohol addiction examining the proportion of alcohol dependence with the A118G allele and comparing the frequency of this allele in alcohol-dependent and control subjects. In addition, the relation between the drinking history of alcohol-dependent patients and the difference in allele frequency of the A118G polymorphism was evaluated.
One hundred patients diagnosed with alcohol dependence, in accordance with DMS-IV criteria, and one hundred of control subjects, are genotyped for the polymorphism.
Information is collected for the alcohol-dependent group on the age at which drinking started, the age of onset of alcohol-related problem, the age of the first admission to a Centre for alcohol-related problems, the average drinking days, monthly average number of drinking days, existence of withdrawal symptoms, the presence of a family drinking history. Clinical data and laboratory data (gGT, AST, ALT, total bilirubin) are collected. Subjects are excluded if they have a major psychiatric disorder. The control group includes healthy subjects without physical or psychiatric illnesses and who do not meet the DMS-IV criteria for alcohol abuse or dependence. To limit the effect of the variability population stratification all the subjects enrolled are of Italian origin (Caucasian).
At date, 87 alcohol dependent patients and 48 control subjects have been genotyping. The G118 allele frequency is 30% in the alcohol dependent patients and 19% in the control group. The 10% increase of the G allele in alcoholics could suggest an association of G allele with alcohol dependency.
Although these data cannot at moment allow any conclusion, we deem of interest to consider also a correlation between nucleotide polymorphism and efficacy of naltrexone treatment.
Di Chiara G et al. (1996). Alcohol. 13, 13-17.
Ray LA et al. (2004). Alcohol Clin Exp Res.28, 1789-95.
Bond C et al. (1998). Proc Natl Acad Sci U S A. 95, 9608-13.
Zhang Y et al. (2005).J Biol Chem. 23, 280, 32618-24. Erratum in: J Biol Chem. (2005), 280, 32618.
A common single nucleotide polymorphism A118G in the mu-opioid receptor gene (OPRM1) has been suggested to contribute to individual variability in alcohol addiction (Ray La et al, 2004). This transition (A→G), leading to an aminoacid substitution (Asn40 to Asp 40) in a highly conserved N-glycosylation site, can cause a significant change in mu-receptor function (Bond et al, 1998; Zhang et al, 2005). Several studies have been conducted in order to identify an association of the A118G with alcohol abuse however they have not provided any unified finding (Mague et al, 2010).
The aim of this study is to investigate the involvement of A118G in alcohol addiction examining the proportion of alcohol dependence with the A118G allele and comparing the frequency of this allele in alcohol-dependent and control subjects. In addition, the relation between the drinking history of alcohol-dependent patients and the difference in allele frequency of the A118G polymorphism was evaluated.
One hundred patients diagnosed with alcohol dependence, in accordance with DMS-IV criteria, and one hundred of control subjects, are genotyped for the polymorphism.
Information is collected for the alcohol-dependent group on the age at which drinking started, the age of onset of alcohol-related problem, the age of the first admission to a Centre for alcohol-related problems, the average drinking days, monthly average number of drinking days, existence of withdrawal symptoms, the presence of a family drinking history. Clinical data and laboratory data (gGT, AST, ALT, total bilirubin) are collected. Subjects are excluded if they have a major psychiatric disorder. The control group includes healthy subjects without physical or psychiatric illnesses and who do not meet the DMS-IV criteria for alcohol abuse or dependence. To limit the effect of the variability population stratification all the subjects enrolled are of Italian origin (Caucasian).
At date, 87 alcohol dependent patients and 48 control subjects have been genotyping. The G118 allele frequency is 30% in the alcohol dependent patients and 19% in the control group. The 10% increase of the G allele in alcoholics could suggest an association of G allele with alcohol dependency.
Although these data cannot at moment allow any conclusion, we deem of interest to consider also a correlation between nucleotide polymorphism and efficacy of naltrexone treatment.
Di Chiara G et al. (1996). Alcohol. 13, 13-17.
Ray LA et al. (2004). Alcohol Clin Exp Res.28, 1789-95.
Bond C et al. (1998). Proc Natl Acad Sci U S A. 95, 9608-13.
Zhang Y et al. (2005).J Biol Chem. 23, 280, 32618-24. Erratum in: J Biol Chem. (2005), 280, 32618.