Sequence variations in the mu-opioid receptor gene (OPRM1) associated with human addiction to heroin

Abstract

Human mu-opioid receptor (OPRM1) is the major site for the analgesic action of most opioid drugs such as morphine, methadone and heroin. It was previously reported that a single nucleotide polymorphism (SNP) in exon1 (c.118A→G) of OPRM1 might modestly alter the affinity in beta-endorphin-Mu interaction. Using denaturing high performance liquid chromatography (DHPLC) the complete coding region of the OPRM1 gene was screened for SNPs in Han-Chinese heroin addicts and normal control. Three novel SNPs were detected, one in exon3, one in intron3 and one in the 3' untranslated region. The SNP c.118A→G reportedly altered the interaction of Mu receptor with opioid had no statistically significant correlation with heroin addition in Han Chinese. However, addicted subjects with the SNP in intron2 (IVS2 +31G→A) tended to show much higher heroin intake dosages than those without this SNP. We also observed that individuals carrying both SNP c.118A→G and IVS2 +31G→A consumed relatively more drugs compared to other addicts. Thus our study further highlights the importance of studing the various regions of the mu opioid receptor gene, coding as well as non-coding, for genetic markers that may be linked to, or directly contribute to opioid drug-seeking behavior.

Novel Linkage Disequilibrium of Single Nucleotide Polymorphisms in the Transcriptional Regulatory Region of .MU.-Opioid Receptor Gene in Japanese Population

“…3) In contrast, the frequency of 118A/G in our result (47.1%; Table 2) demonstrated a greater similarity to the Asian populations than to the European or American ones (Malay, 42.0%; Indian, 47.4%; Chinese, 35.1%; Caucasian, 11.5%; AfricanAmerican, 1.6%); further, the frequency of ivs2ϩ691C/G reported in our result (17.3%; Table 2) demonstrated a greater similarity to the Asian population than to the European and American ones (Malay, 20.5%; Indian, 22.5%; Chinese, 18.3 %; Caucasian, 40.0%; African-American, 50%). [15][16][17] Although SNPs frequency of 118A/G or ivs2ϩ691C/G demonstrated a similar frequency as that observed in Asians, the linkage of 118A/G and ivs2ϩ691C/G observed in Asians was not observed in this study (Malay, DЈϭ0.86; Indian, DЈϭ0.826; Chinese, DЈϭ0.91; our result, DЈϭϪ0.066; Table 3). 18) Therefore, these results suggest that our results obtained from SNPs analysis of OPRM1 in Japanese populations are different from those reported in other countries.…”

The Mu-Opioid Receptor Polymorphism A118G Predicts Cortisol Responses to Naloxone and Stress

“…A recent study demonstrated that this minor allele was linked to more robust subjective responses to alcohol and a positive family history of alcohol use disorders among healthy subjects (Ray and Hutchison, 2004). Still, other studies have found no association between this polymorphism and substance dependence (Bergen et al, 1997;Compton et al, 2003;Crowley et al, 2003;Franke et al, 2001;Gelernter et al, 1999;Hoehe et al, 2000;Ide et al, 2004;Loh et al, 2004;Luo et al, 2003;Sander et al, 1998;Shi et al, 2002). Also, Luo et al (2003) found that while haplotypes at the OPRM1 locus are associated with substance abuse, the A118G polymorphism did not contribute any further information.…”

Linkage disequilibrium and association with methamphetamine dependence/psychosis of μ-opioid receptor gene polymorphisms

“…We found 19 SNPs (Table 1(1)), one dinucleotide polymorphism (DNP), IVS3 þ 6113 (GT) [11][12][13][14][15] and one polynucleotide polymorphism (PNP), a 32-base pair repeat IVS3 þ 8761 (GAC ATA TAT CAT AAT ATA TAT TAT CAT ATT AT) [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] (Table 1( 2)). None of the polymorphisms deviated from the HW expectations.…”

“…[7][8][9] Various studies of the association between frequencies of polymorphisms in the OPRM1 gene and drug dependence on opioids, alcohol or other substances in African-American, Caucasian, Hispanic, Han Chinese and Swedish populations have been reported. [10][11][12][13][14][15][16][17][18] One of these SNPs, A118G, which alters the receptor function, 10 was associated with risk for drug abuse, 14,15 although contradictory data were also reported. 12,13,18 Psychostimulants including methamphetamine (MAP) exert their reinforcing effects by modulating monoaminergic transmission, of which dopamine is supposed to be the most crucial.…”