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rs1799971

Chromosome : 6 , Position: 154039662

Most conditions are affected by anywhere from hundreds to millions of genetic variants (SNPs). A single SNP usually has a minor contribution to a person’s overall genetic risk for a certain condition. That is why you shouldn't consider or act on a SNP in isolation. Instead, we use SNPs to determine polygenic risk scores (PRSs), which are the basis of most health reports.

Reference Allele: A

Alternative Alleles: G

Associated Genes

OPRM1

IPCEF1

CNKSR3

Traits

Trait	Variant	Impact	PMID	Author (year)
Opioid use disorder	G		JAMA Psychiatry	Zhou H (2020)

Summary

The A allele is associated with:

AA=2.16X risk for severe alcoholism (R).
AA combined with less than 12 years of education, increased a persons odds of severe alcoholism by 3.3 times.The researchers suggest that a low education level may magnify the effects of the OPRM1 variant, or that higher education may mask its effects by improving brain function. However, other factors might be responsible for the effect. For example, it is possible that those who attain an education past high school have other characteristics that make them less likely to become addicted to a substance(R).

The G allele is associated with:

G=more pain and opoid usage (R).
G=Mu opioid receptor signaling doesnt work as well. More pain, more opioid usage (still more pain), lower BMI, increased baseline cortisol, better effect with naltrexone, higher risk for alcoholism (R). T
his SNP may also influence the response to opioids such as heroin, codeine or morphine. G=Mu opioid receptor signaling doesn't work as well. More pain, more opioid usage (still more pain), lower BMI,increased baseline cortisol, better effect with naltrexone, higher risk for alcoholism. G= higher consumption of opioids for pain relief(p < 0.00001), but still higher pain scores (p = 0.002)(R).
G= less nausea and vomiting with opioid consumption (p= 0.005) than AA patients during the first 24 hour, but not 48 hour, postoperative period (a meta-analysis totaling 5,902 patients) (R).
G allele is more common inChinese heroin addictscompared to non-addicts (40% vs 29%) in one study [R], but not another [R].
G=stronger cravings for alcohol than carriers of AA.
G=lower obesity (R).
G=increased baseline level of cortisol and greater cortisol responses to opioid receptor blockade with naloxone (healthy subjects,in a population-specific manner) (R)
G=More potent in beta-endorphin binding and receptor activity, but reduced receptor signaling efficacy.Gchanges the amino acid sequence andwas shown to remove a potential N-glycosylation site in the extracellular domain (R). AA=2.16X risk for severe alcoholism (R).

More Information

The G allele seems to decrease opioid receptors. "….increased binding affinity of RXRA transcription factor that may reduce protein translation and hence the number of available receptors to bind with drugs, which may trigger underlying mechanisms for opioids addiction." [R] [R]

In mice programmed with this SNP, G-allele carriers expressed less submissive behavior when challenged by an aggressor and exhibited resilience to social defeat, demonstrated by a lack of subsequent social avoidance and reductions in anhedonia [R].

The G-allele has been linked to submissiveness/social sensitivity and predicted greater speed-dating success for women. However, men with this G-allele were less desirable to their speed-dating partners [R].

G carriers reported higher NEO-Neuroticism scores, particularly in vulnerability to stress and depression (AA: 75; G carriers: 93.6) [R].

G allele feels more pain from social rejection (in addition to physical pain) [R].

Subjects expressing the minor allele (G) had an increased tendency to become engaged in affectionate relationships, and experienced more pleasure in social situations [R].

G carriers, compared with AA homozygotes, showed an overall reduction of baseline μ-opioid receptor availability in regions implicated in pain and emotional regulation [R].

G carriers had less positive effects from the placebo [R].

In response to a sustained painful stimulus, AA homozygotes showed a blunted dopamine response in the nucleus accumbens (NAc) in response to the pain challenge [R].

Results show a significant association between homozygous GG genotype and opioid addiction in Pakistani population [R].

Opioids don't work as well in G carriers (they don't experience as much pain reduction from opioids) [R].

Body mass index (BMI) significantly decreased by the copy of minor allele ''G''. Carriers of the ''G'' allele had a lower risk of obesity (OR=0.75) [R].

Presence of ''G'' allele may lead to greater increases in urge to smoke after a high dose of alcohol [R].

Population Alleles Frequency

ethhicity	frequency
African/African-American	0.0239
Latino/Admixed American	0.195
Ashkenazi Jewish	0.2222
East Asian	0.3374
European	0.1305
Other (population not assigned)	0.163

Frequently Asked Questions

Why Are Alleles for This SNP Different Elsewhere? Major vs. Reference Allele Is My Variant Good or Bad? SNP vs. Mutation

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rs1799971

Associated Genes

Traits

Summary

More Information

Population Alleles Frequency

Frequently Asked Questions

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