Association of Polymorphisms in Pharmacogenetic Candidate Genes (OPRD1, GAL, ABCB1, OPRM1) with Opioid Dependence in European Population: A Case-Control Study

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.

Higher frequency of C.3435 of the ABCB1 gene in patients with tramadol dependence disorder

“…We found no significant association. Meanwhile, another study found that A118G allele has been associated with opioid dependency (21), or plays an important role in dependence on opioid drugs (22). However, others suggested that this evidence is conflicting (23,24).…”

Physiology, Signaling, and Pharmacology of Galanin Peptides and Receptors: Three Decades of Emerging Diversity

“…A significant association of a SNP in intron 2 of the GAL gene and heroin addiction was observed in US Caucasians (Levran et al, 2008), and more recently the involvement of galanin in opioid addiction was further suggested by a candidate gene association study conducted including .100 well phenotyped long-term opioid addicts undergoing opioid maintenance therapy and well matched healthy controls. The most significant association with opioid addiction was for the rs948854 SNP in the GAL gene (Beer et al, 2013).…”

The ABCB1, rs9282564, AG and TT Genotypes and the COMT, rs4680, AA Genotype are Less Frequent in Deceased Patients with Opioid Addiction than in Living Patients with Opioid Addiction

“…The common polymorphism G472A (Val158Met or rs4680) in the catechol-O-methyltransferase (COMT) gene may result in a reduction in the activity of the COMT enzyme [18] for four times, and, consequently, carriers of this variation require lower doses of morphine [19].…”