|(A;G)||2.5||stronger cravings for alcohol. if alcoholic, naltrexone treatment 2x more successful|
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]
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
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[PMID 23302985] The effect of OPRM1 and COMT genotypes on the analgesic response to intravenous fentanyl labor analgesia.
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[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
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[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.