|(A;G)||2.5||stronger cravings for alcohol. if alcoholic, naltrexone treatment 2x more successful|
|?||(A;A) (A;G) (G;G)||28|
The rs1799971(G) allele in exon 1 of the mu opioid receptor OPRM1 gene causes the normal amino acid at residue 40, asparagine (Asn), to be replaced by aspartic acid (Asp). In the literature this SNP is also known as A118G, N40D, or Asn40Asp.
Carriers of at least one rs1799971(G) allele appear to have stronger cravings for alcohol than carriers of two rs1799971(A) alleles, and are thus hypothesized to be more at higher risk for alcoholism. [PMID 17207095]
However, subsequent research results are mixed, and there are other studies both agreeing or disagreeing with this finding [PMID 15525999, PMID 9399694, PMID 12960749]
Among 200+ alcoholics treated with naltrexone, rs1799971(G) carriers receiving the drug (even without behavioral intervention) had an increased percentage of days abstinent (p = .07) and a decreased percentage of heavy drinking days (p = .04) if treated with naltrexone vs. placebo, whereas rs1799971(A;A) homozygotes showed no medication differences. Upon treatment with naltrexone, 87% of rs1799971(G) carriers had a good clinical outcome, compared with only 55% of individuals with the (A;A) genotype (odds ratio, 5.75, CI: 1.88-17.54)[PMID 18250251]
This SNP may also influence the response to opioids such as heroin, codeine or morphine. A 2015 meta-analysis (totaling 5,902 patients) concluded that the carriers of a rs1799971(G) allele consumed more opioids for analgesia (SMD = -0.17, CI:-0.25, -0.10, p < 0.00001), but still reported higher pain scores (p = 0.002) and less nausea and vomiting (odds ratio 1.30, CI:1.08-1.55, p= 0.005) than homozygous (A;A) patients during the first 24 hour, but not 48 hour, postoperative period.[PMID 25794200]
A study of 200 Chinese heroin addicts found increased frequency for the rs1799971(G) allele compared to non-addicts (40% vs 29%) [PMID 11338173]; but another study of Han Chinese addicts found no difference [PMID 11933204].
23andMe blog Alcoholism related
[PMID 19860800] Initial Evidence of an Association Between OPRM1 and Adolescent Alcohol Misuse
[PMID 20112002] A118G Polymorphism of OPRM1 Gene is Associated with Schizophrenia
[PMID 21277709] No evidence of association between 118A>G OPRM1 polymorphism and heroin dependence in a large Bulgarian case-control sample
[PMID 21160491] Haplotype block structure of the genomic region of the mu opioid receptor gene
[PMID 22046326] 'Smoking Genes': A Genetic Association Study
[PMID 22071118] Ethnic-specific meta-analyses of association between the OPRM1 A118G polymorphism and alcohol dependence among Asians and Caucasians
[PMID 16623937] A clinical genetic method to identify mechanisms by which pain causes depression and anxiety.
[PMID 16887046] The mu-opioid receptor gene and smoking initiation and nicotine dependence.
[PMID 18384978] Association of candidate genes with antisocial drug dependence in adolescents.
[PMID 18433502] Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians.
[PMID 18518884] Association between mu-opioid receptor-1 102T>C polymorphism and intermediate type 2 diabetes phenotypes: results from the Quebec Family Study (QFS).
[PMID 18518925] Genetic susceptibility to heroin addiction: a candidate gene association study.
[PMID 18690117] Gene and gene by sex associations with initial sensitivity to nicotine in nonsmokers.
[PMID 18698231] Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues.
[PMID 18725235] Bidirectional translational research: Progress in understanding addictive diseases.
[PMID 19008867] OPRM1 gene is associated with BMI in Uyghur population.
[PMID 19053977] OPRM1 Asn40Asp predicts response to naltrexone treatment: a haplotype-based approach.
[PMID 19103668] Expansion of the human mu-opioid receptor gene architecture: novel functional variants.
[PMID 19258022] Now or Later? An fMRI study of the effects of endogenous opioid blockade on a decision-making network.
[PMID 19335651] Candidate genes for cannabis use disorders: findings, challenges and directions.
[PMID 19775452] Do genetic predictors of pain sensitivity associate with persistent widespread pain?
[PMID 20100356] PCA-based bootstrap confidence interval tests for gene-disease association involving multiple SNPs.
[PMID 20194481] Association of mu-opioid receptor variants and response to citalopram treatment in major depressive disorder.
[PMID 21029375] OPRM1 gene variants modulate amphetamine-induced euphoria in humans.
[PMID 21423693] Effect sizes in experimental pain produced by gender, genetic variants and sensitization procedures.
[PMID 22211341] Variation in OPRM1 and risk of suicidal behavior in drug-dependent individuals.
[PMID 22309038] Possible Association Between OPRM1 Genetic Variance at the 118 Locus and Alcohol Dependence in a Large Treatment Sample: Relationship to Alcohol Dependence Symptoms.
[PMID 22457278] Association of polymorphisms of the mu opioid receptor gene with the severity of HIV infection and response to HIV treatment.
[PMID 22587755] Pharmacogenetically driven treatments for alcoholism: are we there yet?
[PMID 22978509] Convergence of Genome-Wide Association and Candidate Gene Studies for Alcoholism
[PMID 23560613] Association study of OPRM1 polymorphisms with Schizophrenia in Han Chinese population
[PMID 23651028] OPRM1 rs1799971 polymorphism and opioid dependence: evidence from a meta-analysis
[PMID 23803057] Gene Polymorphisms of OPRM1 A118G and ABCB1 C3435T May Influence Opioid Requirements in Chinese Patients with Cancer Pain
[PMID 23454283] Low frequency genetic variants in the μ-opioid receptor (OPRM1) affect risk for addiction to heroin and cocaine
[PMID 24407958] Risky alcohol consumption in young people is associated with the fatty acid amide hydrolase gene polymorphism C385A and affective rating of drug pictures
[PMID 22781865] Testing multiple levels of influence in the intergenerational transmission of alcohol disorders from a developmental perspective: the example of alcohol use promoting peers and mu-opioid receptor M1 variation.
[PMID 22841130] Shared and unique genetic contributions to attention deficit/hyperactivity disorder and substance use disorders: a pilot study of six candidate genes.
[PMID 22954510] Delta and kappa opioid receptor polymorphisms influence the effects of naltrexone on subjective responses to alcohol.
[PMID 23222260] Opioid receptors control viral replication in the airways.
[PMID 23302985] The effect of OPRM1 and COMT genotypes on the analgesic response to intravenous fentanyl labor analgesia.
[PMID 23318993] Opioid receptor polymorphism A118G associated with clinical severity in a drug overdose population.
[PMID 24951719] Genetic Variation of the Mu Opioid Receptor (OPRM1) and Dopamine D2 Receptor (DRD2) is Related to Smoking Differences in Patients with Schizophrenia but not Bipolar Disorder
[PMID 25086307] Endogenous opioid system influences depressive reactions to socially painful targeted rejection life events
[PMID 25715171] OPRM1 genotype and naltrexone response in depressed alcohol-dependent patients
[PMID 25744370] Cis-Expression Quantitative Trait Loci Mapping Reveals Replicable Associations with Heroin Addiction in OPRM1
[PMID 25760804] Naltrexone vs Placebo for the Treatment of Alcohol Dependence: A Randomized Clinical Trial
[PMID 26092968] Influence of the A118G polymorphism of the OPRM1 gene and exon 3 VNTR polymorphism of the DRD4 gene on cigarette craving after alcohol administration
[PMID 26233486] Variations in opioid receptor genes in neonatal abstinence syndrome
[PMID 26392368] Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts
[PMID 26489634] Association of single nucleotide polymorphisms of ABCB1, OPRM1 and COMT with pain perception in cancer patients
[PMID 26581429] The Opposing Roles of IVS2+691 CC Genotype and AC/AG Diplotype of 118A>G and IVS2+691G>C of OPRM1 Polymorphisms in Cold Pain Tolerance Among Opioid-Dependent Malay Males on Methadone Therapy
[PMID 26832728] Genotyping of single nucleotide polymorphisms related to attention-deficit hyperactivity disorder.
[PMID 25986698] Mouse model of OPRM1 (A118G) polymorphism has altered hippocampal function.
[PMID 28349993] Cannabinoid Receptor Type 1 and mu-Opioid Receptor Polymorphisms Are Associated With Cyclic Vomiting Syndrome.
[PMID 29486785] Identification of candidate genes associated with fibromyalgia susceptibility in southern Spanish women: the al-Ándalus project.
[PMID 29913664] A118G polymorphism in the μ-opioid receptor gene and levels of β-endorphin are associated with provoked vestibulodynia and pressure pain sensitivity.
[PMID 31077873] Genetic contribution to PONV risk.
[PMID 31874497] [Effect of opioid-related gene polymorphisms on patients with high-dose opioid-tolerant cancer pain].
[PMID 31961981] Systematic Review and Meta-Analysis of the Moderating Effect of rs1799971 in OPRM1, the Mu-opioid Receptor Gene, on Response to Naltrexone Treatment of Alcohol Use Disorder.
[PMID 32561311] Differential sensitivity of human neurons carrying μ opioid receptor (MOR) N40D variants in response to ethanol.
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