|(A;A)||2.5||significantly increased risk for substance use disorders; possibly higher pain tolerance|
rs324420, also known as c.385C>A or Pro129Thr, is a SNP in the fatty acid amide hydrolase FAAH gene, which has shown associations with some substance use disorders. rs324420(C) encodes the more common Pro, while the (A) allele encodes the Thr.
Among 80 individuals with drug abuse or alcoholism and over 1,000 controls, the odds ratio for risk of problem drug or alcohol use among rs324420(A;A) individuals was 4.5 (CI: 2.2 - 8.4); the odds ratio for risk of street drug use was 2.2 (CI: 1.3–3.7); and the odds ratio for risk of combined street drug use and problem drug/alcohol use was 4.9 (CI: 2.5–9.7)[PMID 12060782]
When this study was pooled with the results of another study of 249 subjects with documented multiple different drug addictions compared to drug free individuals of the same ethnic backgrounds, the results were consistent and even more significant (p = 0.00003). Risk for drug dependence (and drug abuse was associated with rs324420(A;A) homozygotes. [PMID 16972078]
In a study of 40 daily marijuana users who abstained for 24 h and were then presented with a cue-elicited craving paradigm, followed by smoking a marijuana cigarette, rs324420(A) was significantly associated with changes in withdrawal after abstinence and with happiness after smoking marijuana, but was not associated with changes in heart rate after smoking or with changes in craving or other acute effects.[PMID 19002671]
This variant has also been associated with pain insensitivity. In a 2016 study, ~1000 women undergoing surgery for breast cancer were tested for cold and heat pain sensitivity; rs324420(A;A) individuals reported significantly lower cold pain sensitivity and less need for postoperative analgesia.[PMID 26808012] The rs324420(A;C) genotype was also seen in a woman with unusually high pain tolerance, along with a ~8kb heterozygous microdeletion of the adjacent FAAH pseudogene.10.1016/j.bja.2019.02.019
And from a different perspective, a 2016 study published in the Journal of Happiness Studies found "a strong correlation between a nation's happiness and the presence of the (rs324420) A allele in the fatty acid amide hydrolase (FAAH) gene". (news mention; 10.1007/s10902-015-9712-y)
- See also OMIM
[PMID 19958092] Obesity-related dyslipidemia associated with FAAH, independent of insulin response, in multigenerational families of Northern European descent
[PMID 20044928] Mutation screen and association studies for the fatty acid amide hydrolase (FAAH) gene and early onset and adult obesity
[PMID 20010552] Individual and additive effects of the CNR1 and FAAH genes on brain response to marijuana cues
[PMID 22068813] The Fatty Acid Amide Hydrolase (FAAH) Gene Variant rs324420 AA/AC is not Associated with Weight Loss in a 1-Year Lifestyle Intervention for Obese Children and Adolescents
|CLNDBN||Polysubstance abuse, susceptibility to|
|CLNSRC||OMIM Allelic Variant UniProtKB (protein)|
[PMID 15986317] Identification of risk and age-at-onset genes on chromosome 1p in Parkinson disease.
[PMID 17216208] The functional Pro129Thr variant of the FAAH gene is not associated with various fat accumulation phenotypes in a population-based cohort of 5,801 whites.
[PMID 17847002] An LRP8 variant is associated with familial and premature coronary artery disease and myocardial infarction.
[PMID 17991615] Rapid screening for potentially relevant polymorphisms in the human fatty acid amide hydrolase gene using Pyrosequencing.
[PMID 18705688] Marijuana withdrawal and craving: influence of the cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes.
[PMID 19014633] Lack of association of genetic variants in genes of the endocannabinoid system with anorexia nervosa.
[PMID 19053981] The role of fatty acid hydrolase gene variants in inflammatory bowel disease.
[PMID 19335651] Candidate genes for cannabis use disorders: findings, challenges and directions.
[PMID 19659925] Association of CNR1 and FAAH endocannabinoid gene polymorphisms with anorexia nervosa and bulimia nervosa: evidence for synergistic effects.
[PMID 19890266] More aroused, less fatigued: fatty acid amide hydrolase gene polymorphisms influence acute response to amphetamine.
[PMID 20033240] Eating disorders: the current status of molecular genetic research.
[PMID 20054193] Evaluating the association of FAAH common gene variation with childhood, adult severe obesity and type 2 diabetes in the French population.
[PMID 20080186] Investigation of CNR1 and FAAH endocannabinoid gene polymorphisms in bipolar disorder and major depression.
[PMID 20631561] Endocannabinoid Pro129Thr FAAH functional polymorphism but not 1359G/A CNR1 polymorphism is associated with antipsychotic-induced weight gain.
[PMID 21477106] Association of genetic variation in cannabinoid mechanisms and gastric motor functions and satiation in overweight and obesity.
[PMID 21803011] Pharmacogenetic trial of a cannabinoid agonist shows reduced fasting colonic motility in patients with nonconstipated irritable bowel syndrome.
[PMID 22288893] Randomized pharmacodynamic and pharmacogenetic trial of dronabinol effects on colon transit in irritable bowel syndrome-diarrhea.
[PMID 22688188] Convergent translational evidence of a role for anandamide in amygdala-mediated fear extinction, threat processing and stress-reactivity.
[PMID 23048207] Distinct and replicable genetic risk factors for acute respiratory distress syndrome of pulmonary or extrapulmonary origin
[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 23333123] Genetic variation in the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH) and their influence on weight loss and insulin resistance under a high monounsaturated fat hypocaloric diet.
[PMID 25731744] FAAH genetic variation enhances fronto-amygdala function in mouse and human
[PMID 27394933] Genetic variation in FAAH is associated with cannabis use disorders in a young adult sample of Mexican Americans.
[PMID 30949563] FAAH genotype, CRFR1 genotype, and cortisol interact to predict anxiety in an aging, rural Hispanic population: A Project FRONTIER study.