Our results do not provide evidence that the common Asn40Asp substitution polymorphism of the OPRM gene contributes a major effect to the pathogenesis of alcohol dependence.
Common to this category was a characteristic pattern of sequence variants [-1793T-->A, -1699Tins, -1320A-->G, -111C-->T, +17C-->T (A6V)], which was associated with substance dependence.
In the present investigation we hypothesized the A118G (Asn40Asp) polymorphism of the mu-opioid receptor gene (OPRM1) as a particular vulnerability factor for heroin and alcohol dependence.
In both patient samples and by both methods we were unable to corroborate the hypothesis of OPRM1 A118G polymorphism as a particular risk factor for any kind of substance dependence including opioid addiction.
In both patient samples and by both methods we were unable to corroborate the hypothesis of OPRM1 A118G polymorphism as a particular risk factor for any kind of substance dependence including opioid addiction.
Previously, two single nucleotide polymorphisms (SNPs), OPRD1 921T > C and 80G > T, of the human delta opioid receptor gene were used in population-based studies of heroin dependence.
For the A118G polymorphism, we found significant differences in allele and genotype frequencies between different ethnic groups and highly significant association with heroin dependence in Indians for both genotype distribution (p = 0.024) and allele frequency (p = 0.009).
Eight single nucleotide polymorphisms (SNPs) at the OPRM1 locus, i.e., -2044C/A, -1793T/A, -1699insT, -1469T/C, -1320A/G, -111C/T, +17C/T (Ala6Val), and +118A/G (Asn40Asp) were genotyped in 676 subjects: 318 EA subjects and 124 AA subjects with substance dependence, and 179 EA normal controls, and 55 AA normal controls.
Four of the variants [-1793T/A, -1699insT, -1320A/G, and -111C/T] are in virtually complete linkage disequilibrium (LD) to compose a sequence pattern, which does not associate with any of the seven categories of substance dependence.
Patients homozygous for the variant G allele of the 118 A > G polymorphism (n = 4) needed more morphine to achieve pain control, compared to heterozygous (n = 17) and homozygous wild-type (n = 78) individuals.
These results suggest that having one or two copies of the A118G allele is common among Koreans and may be an important genetic factor in the etiology of alcohol dependence and the frequency of alcohol consumption.
Functional alleles that alter alcoholism-related intermediate phenotypes include common alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 variants that cause the aversive flushing reaction; catechol-O-methyltransferase (COMT) Val158Met leading to differences in three aspects of neurobiology: executive cognitive function, stress/anxiety response, and opioid function; opioid receptor micro1 (OPRM1) Asn40Asp, which may serve as a gatekeeper molecule in the action of naltrexone, a drug used in alcoholism treatment; and HTTLPR, which alters serotonin transporter function and appears to affect stress response and anxiety/dysphoria, which are factors relevant to initial vulnerability, the process of addiction, and relapse.
Functional alleles that alter alcoholism-related intermediate phenotypes include common alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 variants that cause the aversive flushing reaction; catechol-O-methyltransferase (COMT) Val158Met leading to differences in three aspects of neurobiology: executive cognitive function, stress/anxiety response, and opioid function; opioid receptor micro1 (OPRM1) Asn40Asp, which may serve as a gatekeeper molecule in the action of naltrexone, a drug used in alcoholism treatment; and HTTLPR, which alters serotonin transporter function and appears to affect stress response and anxiety/dysphoria, which are factors relevant to initial vulnerability, the process of addiction, and relapse.
Controlling for demographic features and substance dependence diagnosis, analyses examined the allelic association of Asn40Asp with the five personality dimensions.
Functional alleles that alter alcoholism-related intermediate phenotypes include common alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 variants that cause the aversive flushing reaction; catechol-O-methyltransferase (COMT) Val158Met leading to differences in three aspects of neurobiology: executive cognitive function, stress/anxiety response, and opioid function; opioid receptor micro1 (OPRM1) Asn40Asp, which may serve as a gatekeeper molecule in the action of naltrexone, a drug used in alcoholism treatment; and HTTLPR, which alters serotonin transporter function and appears to affect stress response and anxiety/dysphoria, which are factors relevant to initial vulnerability, the process of addiction, and relapse.
Functional alleles that alter alcoholism-related intermediate phenotypes include common alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 variants that cause the aversive flushing reaction; catechol-O-methyltransferase (COMT) Val158Met leading to differences in three aspects of neurobiology: executive cognitive function, stress/anxiety response, and opioid function; opioid receptor micro1 (OPRM1) Asn40Asp, which may serve as a gatekeeper molecule in the action of naltrexone, a drug used in alcoholism treatment; and HTTLPR, which alters serotonin transporter function and appears to affect stress response and anxiety/dysphoria, which are factors relevant to initial vulnerability, the process of addiction, and relapse.