Lack of association between the A118G polymorphism of the mu opioid receptor gene (OPRM1) and opioid dependence: A meta-analysis

Janet K Coller, Julia Beardsley, James Bignold, Yibai Li, Florence Merg, Thomas Sullivan, Timothy C Cox, Andrew A Somogyi, Janet K Coller, Julia Beardsley, James Bignold, Yibai Li, Florence Merg, Thomas Sullivan, Timothy C Cox, Andrew A Somogyi

Abstract

Mu opioid receptor (OPRM1) gene variants, particularly the common A118G single nucleotide polymorphism (SNP), are among the most frequently studied candidate genes associated with opioid dependence. However, despite numerous case-control studies and meta-analyses, no definitive conclusion has been reached regarding the association of the A118G SNP and risk of developing opioid dependence. This study aimed to resolve this discrepancy by reinvestigating the association between A118G SNP allelic, and for the first time, genotype frequencies and opioid dependence. A meta-analysis of sixteen case-control studies of opioid dependence was performed with a total of 5169 subjects. No association between the A118G allele (P = 0.23) and genotype (P = 0.34) frequencies and opioid dependence was found. However, significant heterogeneity between studies precluded highly definitive conclusions. In addition, the possibility that other OPRM1 SNPs albeit rarer may influence the risk of opioid dependence remains to be investigated at this level. Nonetheless, despite no evidence of a direct association with risk of dependence, A118G may still influence the pharmacological response to opioids impacting on an individual's dosage requirements.

Keywords: A118G genotype; meta-analysis; mu opioid receptor; opioid dependence.

Figures

Figure 1
Figure 1
Forest plot depicting the odds ratios (OR) and 95% confidence interval (CI) of each of the 13 studies investigating the association between A118G OPRM1 genotype frequencies and opioid dependence. The solid line represents an OR of 1 and the stippled line represents the pooled OR.
Figure 2
Figure 2
Begg’s funnel plot of the 13 studies investigating the association between A118G OPRM1 genotype frequencies and opioid dependence.
Figure 3
Figure 3
Forest plot depicting the odds ratios (OR) and 95% confidence interval (CI) of each of the 13 studies investigating the association between A118G OPRM1 genotype frequencies and opioid dependence stratified as majority Caucasian and Asian ethnic groups. The solid line represents an OR of 1 and the stippled line represents the pooled OR.
Figure 4
Figure 4
Forest plot depicting the odds ratios (OR) and 95% confidence interval (CI) of each of the 16 studies investigating the association between A118G OPRM1 allele frequencies and opioid dependence. The solid line represents an OR of 1 and the stippled line represents the pooled OR, P = 0.000 equivalent to P < 0.0001.
Figure 5
Figure 5
Begg’s funnel plot of the 16 studies investigating the association between A118G OPRM1 allele frequencies and opioid dependence.
Figure 6
Figure 6
Forest plot depicting the odds ratios (OR) and 95% confidence interval (CI) of each of the 16 studies investigating the association between A118G OPRM1 allele frequencies and opioid dependence stratified as majority Caucasian and Asian ethnic groups. The solid line represents an OR of 1 and the stippled line represents the pooled OR, P = 0.000 equivalent to P

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