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  1. A118G mu opioid receptor polymorphism among drug addicts in Malaysia
    Nagaya D, Ramanathan S, Ravichandran M, Navaratnam V
    J Integr Neurosci, 2012 Mar;11(1):117-22.
    PMID: 22744787
    Drug addiction is an important social problem in many countries. Genetic and environmental factors contribute to the predisposition of drug addiction. Genetic variations at the μ opioid receptor (OPRM1) gene locus have been associated with opiate addiction. The present study aims to delineate the frequency of A118G allele of OPRM1 among Malaysian subjects. The frequency of A allele and G allele were 51% and 49%, respectively for addicts and about 73% and 27% respectively for healthy volunteers. The frequency of G allele was 1.77-fold higher in addicts by odds ratio calculation at 95% Cl, which indicate the G allele to be strongly associated with addiction X(2) = 15.31,P < 0.0001; odds ratio 2.51; 95% Cl (1.575-3.994), compared to healthy volunteers. A significant association was observed between A118G polymorphism in μ opioid receptor gene and drug addiction.
  2. An analysis of genetic association in opioid dependence susceptibility
    Nagaya D, Zahari Z, Saleem M, Yahaya BH, Tan SC, Yusoff NM
    J Clin Pharm Ther, 2018 Feb;43(1):80-86.
    PMID: 28656735 DOI: 10.1111/jcpt.12585
    WHAT IS KNOWN: Drug addiction is a novelty-seeking personality trait that is associated with the candidate genes OPRD1 (opioid delta receptors), OPRK1 (opioid kappa receptors) and PDYN (prodynorphin). However, associations between single nucleotide polymorphisms (SNPs) rs1042114 (80G>T) of the OPRD1 gene, rs702764 (843 A>G) of the OPRK1 gene, and rs910080 (3' UTR _743T>C), rs1997794 (5' UTR -381A>G) and rs1022563 (3' UTR) of the PDYN gene and novelty seeking remain controversial as reported results have not been reproducible.

    OBJECTIVE: The goal of this study was to determine the frequencies of SNPs rs1042114, rs702764, rs1997794, rs1022563 and rs910080 in the Malaysian population and to study their association with opioid dependence in Malaysian Malays.

    METHODS: A total of 459 Malay male with opioid dependence and 543 healthy male (controls) subjects were included in this study. SNPs were genotyped using the TaqMan SNP genotyping assay. Statistical analysis was performed using Golden Helix SVS software suite to identify the distribution of allele and genotype frequencies, and SNP-SNP interactions were also analysed in this study.

    RESULTS AND DISCUSSION: SNP rs1042114 in the OPRD1 gene is strongly associated with opiate addiction (P=.0001). In individuals homozygous for this risk allele, the likelihood of opiate addiction is increased by a factor 1.62 (95% confidence interval (CI) 1.412-1.875). Polymorphic alleles at SNP rs702764 of OPRK1 were not associated with opioid dependence. A significant association between opioid dependence and SNP rs910080 of PDYN (P=.0217) was detected, but there was no association for SNPs rs199774 and rs1022563. A significant interaction was also identified between homozygous wild-type genotype TT of rs702764 with the risk genotypes TG/GG of rs1042114 (odds ratio (OR)=2.111 (95% CI 1.227-3.631), P=.0069) and with the risk genotypes GA/AA of rs910080 (OR=1.415 (95% CI 1.04-1.912), P=.0239).

    WHAT IS NEW AND CONCLUSION: The results indicate that SNPs rs1042114 and rs910080 contribute to vulnerability to opioid dependence in the Malaysian Malay population. These results will help us to understand the effect of the SNPs and the SNP-SNP interaction on opioid dependence and may assist in efforts to screen vulnerable individuals and match them with individually tailored prevention and treatment strategies.

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