Association of an Asn40Asp (A118G) polymorphism in the mu-opioid receptor gene with substance dependence: a meta-analysis.
BACKGROUND
The mu-opioid receptor has been implicated in the pathogenesis of dependence on opioids, alcohol, nicotine, and cocaine. Studies examining the association of the mu-opioid receptor gene (genetic locus OPRM1) with substance dependence (SD) have focused on the Asn40Asp (A118G) single nucleotide polymorphism (SNP).


METHODS
We used meta-analysis to examine the literature on the association of Asn40Asp with SD. Twenty-two articles describing 28 distinct samples and over 8000 subjects were included. A variety of factors (i.e., ethnicity, type of SD, rigor with which controls were screened, severity of SD among cases) were examined as potential moderators of the association.


RESULTS
Four studies showed a significantly higher frequency of the Asp40 allele among SD cases, while three studies showed a significantly higher frequency of the Asp40 allele among controls. There was no significant association between Asn40Asp and SD (OR=1.01, 95%CI=0.86-1.19), nor was there substantial evidence of a moderator effect.


CONCLUSIONS
The Asn40Asp SNP in OPRM1 does not appear to affect risk for SD. Additional research is needed to determine whether these findings reflect no role for OPRM1 in determining risk for SD or whether another polymorphism in the gene influences receptor function and risk for SD.
Arias
Albert
A
Alcohol Research Center, Department of Psychiatry, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-2103, USA.
Feinn
Richard
R
Kranzler
Henry R
HR
D000437:Alcoholism / Q000235:genetics*; D001216:Asparagine / Q000235:genetics*; D001224:Aspartic Acid / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D012306:Risk; D019966:Substance-Related Disorders / Q000235:genetics*
C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D001224:Aspartic Acid; D001216:Asparagine