rs1800497, a SNP also known as the TaqIA (or Taq1A) polymorphism of the dopamine D2 receptor DRD2 gene (even though it is actually located over 10,000bp downstream of the gene), gives rise to the DRD2*A1 allele. This allele (rs1800497(T)) is associated with a reduced number of dopamine binding sites in the brain [PMID 9672901], and has been postulated to play a role in alcoholism, smoking, and certain neuropsychiatric disorders.
The reduced number of dopamine binding sites may play a role in nicotine addiction by causing an "understimulated" state that can be relieved by smoking (and/or use of other drugs). [PMID 8873216]
A wide variety of reports have been published over more than ten years either linking rs1800497 to aspects of nicotine use and smoking cessation success, or finding no such association. A meta-analysis of 41 such studies published in 2004 concluded that overall the association of rs1800497 with such phenomena was statistically weak. [PMID 15370155] This same group recently (2009) published a study showing no association between rs1800497 and improved response to nicotine replacement therapy (NRT), contrary to their previous study.[PMID 19273465]
More recently, a relatively large study of over 700 patients attempting to kick their smoking habit using the drug bupropion determined that smokers homozygous for the A2/A2 genotype were more successful than A1/A2 or A1/A1 individuals. The A2/A2 smokers were more than three times as likely, relative to placebo, to be abstinent at end of treatment (35.2% vs. 15.1%; odds ratio = 3.25, CI: 2.00-5.28) and at 6 months of follow-up (26.7% vs. 12.2%; odds ratio = 2.81, CI: 1.66-4.77), whereas not so much by 12 months (16.3% vs. 10.7%; OR = 1.70, CI: 0.95-3.05). Basically, A1/A2 and A1/A1 genotype smokers didn't gain anything from using bupropion versus placebo; bupropion only helped A2/A2 genotypes stop smoking. [PMID 18058343]
In a study of individuals in the Polyp Prevention Trial with any, multiple (>/=2) or advanced colorectal adenoma recurrence after 4 years, compared to those without adenoma recurrence, rs1800497(T;T) individuals were significantly associated with all advanced adenoma recurrence (odds ratio 2.40, CI: 1.11-5.20). The authors speculate this increased risk of adenoma recurrence (and an association with colorectal cancer) may be related to SNP-associated differences in alcohol and fat intake.[19065655?dopt=Abstract PMID 19065655]
A 2014 preliminary study links an individual's ANKK1 rs1800497 genotype as likely to experience greater positive subjective effects following cocaine exposure, including greater 'high' and 'like', and these individuals may have increased vulnerability to continue using cocaine or they may be at greater risk to relapse during periods of abstinence. The study states that replication of these findings is necessary to confirm these findings.[PMID 24528631]
SNPs rs6276, rs6277, and rs1800497) in the human DRD2 gene are associated with decreased D2R expression and function, as well as high blood pressure. Data supports the hypothesis that D2R function has protective effects in human renal proximal tubule cells hRPTCs and suggest that carriers of these SNPs may be prone to chronic renal disease and high blood pressure. [PMID 24379187]
SNPs, rs1800497 and rs2283265, located near and within the dopamine receptor 2 DRD2 gene, respectively, were significantly associated with improvements during working memory training (p < .003 and p < .0004, respectively). [PMID 24001007]
[PMID 18698520] A small (54 patient) study of patients with traumatic brain injury concluded that carriers of rs1800497(A) alleles recover slower as assessed by memory and attention tests.
23andMe blog diminished pleasure response from food[PMID 19344737] Associations of the DRD2 TaqIA Polymorphism with Impulsivity and Substance Use: Preliminary Results from a Clinical Sample of Adolescents.
[PMID 19373123] Genetic variants altering dopamine D2 receptor expression or function modulate the risk of opiate addiction and the dosage requirements of methadone substitution
[PMID 19796663] Influence of DRD2 and ANKK1 genotypes on apomorphine-induced growth hormone (GH) response in alcohol-dependent patients
[PMID 19925838] Parental Control and the Dopamine D2 Receptor Gene (DRD2) interaction on Emotional Eating in Adolescence
[PMID 19512960] Genetic diagnostics of functional variants of the human dopamine D2 receptor gene
[PMID 20350135] Prospective association of dopamine-related polymorphisms with smoking cessation in general care
[PMID 21084795] Acute Intravenous Synaptamine Complex Variant KB220™ "Normalizes" Neurological Dysregulation in Patients During Protracted Abstinence From Alcohol and Opiates as Observed Using Quantitative Electroencephalographic and Genetic Analysis for Reward Polymorphisms: Part 1, Pilot Study with 2 Case Reports
[PMID 21244440] Risky Alcohol Use in Adolescence: The Role of Genetics (DRD2, SLC6A4) and Coping Motives
[PMID 21456129] Single nucleotide polymorphism genotyping and point mutation detection by ligation on microarrays
[PMID 21540761] Association between DRD2/ANKK1 Taq1A genotypes, depression and smoking cessation with nicotine replacement therapy
[PMID 20505554] Association study between the DAT1, DBH and DRD2 genes and cocaine dependence in a Spanish sample
[PMID 21714067] Association between polymorphisms of DRD2 and DRD4 and opioid dependence: Evidence from the current studies
[PMID 22046326] 'Smoking Genes': A Genetic Association Study
[PMID 22438994] Dopaminergic Polymorphisms Associated with Time-on-Task Declines and Fatigue in the Psychomotor Vigilance Test
[PMID 22615781] Candidate Gene-Based Association Study of Antipsychotic-Induced Movement Disorders in Long-Stay Psychiatric Patients: A Prospective Study
[PMID 22541053] TaqIA polymorphism in dopamine D2 receptor gene complicates weight maintenance in younger obese patients.
[PMID 22579533] Binge eating disorder and the dopamine D2 receptor: Genotypes and sub-phenotypes.
|Disease||Dopamine receptor d2, AllHighlyPenetrant|
|CLNDBN||Dopamine receptor d2, reduced brain density of, AllHighlyPenetrant|
|CLNSRC||Emory University, OMIM Allelic Variant|
[PMID 15146457] Identification and characterization of ANKK1: a novel kinase gene closely linked to DRD2 on chromosome band 11q23.1.
[PMID 16380908] Preferential transmission of paternal alleles at risk genes in attention-deficit/hyperactivity disorder.
[PMID 17135598] No evidence for a major role of polymorphisms during bupropion treatment.
[PMID 17417059] A dopamine D2 receptor gene-related polymorphism is associated with schizophrenia in a Spanish population isolate.
[PMID 17466074] Genetic polymorphisms in dopamine-related genes and smoking cessation in women: a prospective cohort study.
[PMID 17483451] Gene-gene interaction associated with neural reward sensitivity.
[PMID 17585060] Genetic variants in the DRD2 gene moderate the relationship between stressful life events and depressive symptoms in adults: cardiovascular risk in young Finns study.
[PMID 17908762] Dopamine receptor D2 gene Taq1A (C32806T) polymorphism modifies the relationship between birth weight and educational attainment in adulthood: 21-year follow-up of the Cardiovascular Risk in Young Finns study.
[PMID 18077373] Polymorphisms in human dopamine D2 receptor gene affect gene expression, splicing, and neuronal activity during working memory.
[PMID 18154681] A lesson not learned: allele misassignment.
[PMID 18305461] Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety.
[PMID 18351593] DRD3, but not COMT or DRD2, genotype affects executive functions in healthy and first-episode psychosis adolescents.
[PMID 18354387] Significant association of ANKK1 and detection of a functional polymorphism with nicotine dependence in an African-American sample.
[PMID 18366720] Association of dopaminergic pathway gene polymorphisms with chronic renal insufficiency among Asian Indians with type-2 diabetes.
[PMID 18690117] Gene and gene by sex associations with initial sensitivity to nicotine in nonsmokers.
[PMID 18715757] Genetic associations with schizophrenia: meta-analyses of 12 candidate genes.
[PMID 18781856] Genetic underpinnings of tardive dyskinesia: passing the baton to pharmacogenetics.
[PMID 19238152] Interaction between dopamine D2 receptor genotype and parental rule-setting in adolescent alcohol use: evidence for a gene-parenting interaction.
[PMID 19258022] Now or Later? An fMRI study of the effects of endogenous opioid blockade on a decision-making network.
[PMID 19285111] C957T polymorphism of the human dopamine D2 receptor gene predicts extrastriatal dopamine receptor availability in vivo.
[PMID 19309284] Haplotype diversity and linkage disequilibrium at DRD2 locus--a study on four population groups of Andhra Pradesh, India.
[PMID 19321766] Dopamine DRD2 polymorphism alters reversal learning and associated neural activity.
[PMID 19470168] NPAS2 and PER2 are linked to risk factors of the metabolic syndrome.
[PMID 19526298] The ANKK1 kinase gene and psychiatric disorders.
[PMID 19664686] Potential association of DRD2 and DAT1 genetic variation with heroin dependence.
[PMID 19669131] Clinical and pharmacogenetic determinants for the discontinuation of non-ergoline dopamine agonists in Parkinson's disease.
[PMID 19693267] Financial and psychological risk attitudes associated with two single nucleotide polymorphisms in the nicotine receptor (CHRNA4) gene.
[PMID 19793394] Haplotype frequencies at the DRD2 locus in populations of the East European Plain.
[PMID 20138949] A genetic schizophrenia-susceptibility region located between the ANKK1 and DRD2 genes.
[PMID 20146828] Dopamine D2 receptor polymorphisms and susceptibility to alcohol dependence in Indian males: a preliminary study.
[PMID 20180986] CLOCK is suggested to associate with comorbid alcohol use and depressive disorders.
[PMID 20191112] The Genetics of Anorexia Nervosa: Current Findings and Future Perspectives.
[PMID 20199723] [DRD2/ANKK1 Taq IA polymorphism and early infant temperament].
[PMID 20205808] Association between dopaminergic polymorphisms and borderline personality traits among at-risk young adults and psychiatric inpatients.
[PMID 20446882] Do candidate genes discriminate patients with an autism spectrum disorder from those with attention deficit/hyperactivity disorder and is there an effect of lifetime substance use disorders?
[PMID 20452395] Association of functional variants in the dopamine D2-like receptors with risk for gambling behaviour in healthy Caucasian subjects.
[PMID 20567893] Association between polymorphisms of the dopamine receptor D2 and catechol-o-methyl transferase genes and cognitive function.
[PMID 21097659] Interaction effect of functional variants of the BDNF and DRD2/ANKK1 gene is associated with alexithymia in healthy human subjects.
[PMID 21162693] Pharmacogenetics and antipsychotics: therapeutic efficacy and side effects prediction.
[PMID 21172166] Pharmacogenetics of antidepressant response.
[PMID 21645585] Resting posterior minus frontal EEG slow oscillations is associated with extraversion and DRD2 genotype.
[PMID 21663922] Association of DRD2 and DRD3 polymorphisms with Parkinson's disease in a multiethnic consortium.
[PMID 21997315] ANKK1/DRD2 locus variants are associated with rimonabant efficacy in aiding smoking cessation: pilot data.
[PMID 22244514] Sensorimotor gating and D2 receptor signalling: evidence from a molecular genetic approach.
[PMID 22259185] Additive effects of serotonergic and dopaminergic polymorphisms on trait impulsivity.
[PMID 22382052] A DRD2 and ANKK1 haplotype is associated with nicotine dependence.
[PMID 22531292] Sex-specific influence of DRD2 on ADHD-type temperament in a large population-based birth cohort.
[PMID 22582185] DRD2 C957T and TaqIA Genotyping Reveals Gender Effects and Unique Low-Risk and High-Risk Genotypes in Alcohol Dependence.
[PMID 22978509] Convergence of Genome-Wide Association and Candidate Gene Studies for Alcoholism
|qualified_impact||Insufficiently evaluated pathogenic|
[PMID 23683269] DRD2/ANKK1 Taq1A polymorphism (rs1800497) has opposing effects on D2/3 receptor binding in healthy controls and patients with major depressive disorder
[PMID 23741438] Linguistic Grammar Learning and DRD2-TAQ-IA Polymorphism
[PMID 23840506] Multivariate analysis of dopaminergic gene variants as risk factors of heroin dependence
[PMID 23941313] Influence of a Dopamine Pathway Additive Genetic Efficacy Score on Smoking Cessation: Results from Two Randomized Clinical Trials of Bupropion
[PMID 24283216] Association analyses for dopamine receptor gene polymorphisms and weight status in a longitudinal analysis in obese children before and after lifestyle intervention
[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 24528631] A variant in ANKK1 modulates acute subjective effects of cocaine: a preliminary study.
[PMID 24512061] Living in the moment: Effects of time perspective and emotional valence of episodic thinking on delay discounting.
[PMID 24379187] Single-nucleotide polymorphisms of the dopamine d2 receptor increase inflammation and fibrosis in human renal proximal tubule cells.
[PMID 24001007] Polymorphisms in the dopamine receptor 2 gene region influence improvements during working memory training in children and adolescents.
[PMID 22683321] Epistatic interactions implicating dopaminergic genes in bulimia nervosa (BN): relationships to eating- and personality-related psychopathology.
[PMID 22698582] DRD2/ANKK1 TaqIA and SLC6A3 VNTR polymorphisms in alcohol dependence: association and gene-gene interaction study in a population of Central Italy.
[PMID 22728571] DRD2/ANKK1 TaqI A genotype moderates the relationship between alexithymia and the relative value of alcohol among male college binge drinkers.
[PMID 22761283] Multigene interactions and the prediction of depression in the Wisconsin Longitudinal Study.
[PMID 22875483] Identification of a novel ANKK1 and other dopaminergic (DRD2 and DBH) gene variants in migraine susceptibility.
[PMID 22949583] Pharmacogenetic smoking cessation intervention in a health care setting: a pilot feasibility study.
[PMID 23118020] DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia.
[PMID 23635803] ANKK1 and DRD2 pharmacogenetics of disulfiram treatment for cocaine abuse.
[PMID 23644918] Candidate glutamatergic and dopaminergic pathway gene variants do not influence Huntington's disease motor onset.