Abstract
It is becoming increasingly evident that genetic variants contribute to the development of opioid addiction. An elucidation of these genetic factors is crucial for a better understanding of this chronic disease and may help to develop novel therapeutic strategies. In recent years, several candidate genes were implicated in opioid dependence. However, most study findings have not been replicated and additional studies are required before reported associations can be considered robust. Thus, the major objective of this study was to replicate earlier findings and to identify new genetic polymorphisms contributing to the individual susceptibility to opioid addiction, respectively. Therefore, a candidate gene association study was conducted including 142 well-phenotyped long-term opioid addicts undergoing opioid maintenance therapy and 142 well-matched healthy controls. In both study groups, 24 single nucleotide polymorphisms predominantly located in pharmacogenetic candidate genes have been genotyped using an accurate mass spectrometry based method. The most significant associations with opioid addiction (remaining significant after adjustment for multiple testing) were observed for the rs948854 SNP in the galanin gene (GAL, p = 0.001) and the rs2236861 SNP in the delta opioid receptor gene (OPRD1, p = 0.001). Moreover, an association of the ATP binding cassette transporter 1 (ABCB1) variant rs1045642 and the Mu Opioid receptor (OPRM1) variant rs9479757 with opioid addiction was observed. The present study provides further support for a contribution of GAL and OPRD1 variants to the development of opioid addiction. Furthermore, our results indicate a potential contribution of OPRM1 and ABCB1 SNPs to the development of this chronic relapsing disease. Therefore it seems important that these genes are addressed in further addiction related studies.
Highlights
The etiology of opioid addiction is complex and involves environmental, psychological as well as drug induced factors [1,2]
The patient group consisted of 80 individuals undergoing methadone maintenance treatment (MMT) and 62 individuals undergoing buprenorphine maintenance treatment (BMT)
Regarding the OPRM1 rs9479757 single nucleotide polymorphism (SNP) we found a significantly lower GA genotype frequency (p = 0.028, χ2 = 4.81, df = 1) and a higher GG genotype frequency in the patients compared to the controls
Summary
The etiology of opioid addiction is complex and involves environmental, psychological as well as drug induced factors [1,2]. Several candidate genes have been implicated in opioid dependence. One of the most extensively studied candidates is the mu opioid receptor gene (OPRM1) and its functional single nucleotide polymorphism (SNP) rs1799971 (A118G), which has been reported to affect the individual vulnerability to opioid dependence, not in all studies [5]. Study findings have often not been replicated or are inconsistent between studies and the overall knowledge on genetic factors influencing the development of opioid addiction is still limited [3,5,6]. Further research is required to identify genetic variants contributing to the development of opioid addiction, to confirm tentative genetic associations and to improve the neurobiological understanding of opioid dependence [1,6]
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