Rs1799971

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.

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)

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.

A study of 200 Chinese heroin addicts found increased frequency for the rs1799971(G) allele compared to non-addicts (40% vs 29%) ; but another study of Han Chinese addicts found no difference.

23andMe blog Alcoholism related
 * rs1799971(A;A) severe alcoholism 2x
 * rs1799732(I;I) severe alcoholism 1.85x

A clinical genetic method to identify mechanisms by which pain causes depression and anxiety.

The mu-opioid receptor gene and smoking initiation and nicotine dependence.

Association of candidate genes with antisocial drug dependence in adolescents.

Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians.

Association between mu-opioid receptor-1 102T>C polymorphism and intermediate type 2 diabetes phenotypes: results from the Quebec Family Study (QFS).

Genetic susceptibility to heroin addiction: a candidate gene association study.

Gene and gene by sex associations with initial sensitivity to nicotine in nonsmokers.

Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues.

Bidirectional translational research: Progress in understanding addictive diseases.

OPRM1 gene is associated with BMI in Uyghur population.

OPRM1 Asn40Asp predicts response to naltrexone treatment: a haplotype-based approach.

Expansion of the human mu-opioid receptor gene architecture: novel functional variants.

Now or Later? An fMRI study of the effects of endogenous opioid blockade on a decision-making network.

Candidate genes for cannabis use disorders: findings, challenges and directions.

Do genetic predictors of pain sensitivity associate with persistent widespread pain?

PCA-based bootstrap confidence interval tests for gene-disease association involving multiple SNPs.

Association of mu-opioid receptor variants and response to citalopram treatment in major depressive disorder.

OPRM1 gene variants modulate amphetamine-induced euphoria in humans.

Effect sizes in experimental pain produced by gender, genetic variants and sensitization procedures.

Variation in OPRM1 and risk of suicidal behavior in drug-dependent individuals.

Possible Association Between OPRM1 Genetic Variance at the 118 Locus and Alcohol Dependence in a Large Treatment Sample: Relationship to Alcohol Dependence Symptoms.

Association of polymorphisms of the mu opioid receptor gene with the severity of HIV infection and response to HIV treatment.

Pharmacogenetically driven treatments for alcoholism: are we there yet?

Naltrexone Treatment Response