rs6277

A=need higher dose of methadone (R). The A allele needed higher methadone doses than noncarriers and it was associated with a longer time to reach the maximum methadone dose (P=0.025) (R). AA=decreased dopamine signaling (R). G allele was associated with 1.42X higher risk of schizophrenia (p<0.00005) [R]. GG=1.6X increased risk for Schizophrenia (p<0.00005) [R]. G allele is associated with PTSD (p = 0.021) [R].

AA=tend to be better NoGo learners(R).

Trials that rewarded faster responses measured Go learning. Trials that rewarded holding off on the action of button pushing measured NoGo learning (R).

A allele =lower DRD2 [R]. The A allele needed higher methadone doses than noncarriers and it was associated with a longer time to reach the maximum methadone dose (P=0.025) (R).

The effects of dopamine in the basal ganglia have been shown in experiments that use drugs to raise or lower levels of the neurotransmitter in the brain. Higher dopamine levels help people learn to repeat rewarding behaviors, while lower dopamine leads to better learning from bad experiences. In a game where A usually yields more points than B, people with boosted dopamine levels learn to choose A. People with decreased dopamine levels learn to avoid B (R).

In non-medicated test subjects, genetic variations that influence dopamine signaling in the basal ganglia also impact so-called Go (choose A) and NoGo learning (avoid B)(R).

    [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 20046399] Genetic polymorphisms in dopamine- and serotonin-related genes and treatment responses to risperidone and perospirone [PMID 19512960] Genetic diagnostics of functional variants of the human dopamine D2 receptor gene [PMID 20421849] Habituation in prepulse inhibition is affected by a polymorphism on the NMDA receptor 2B subunit gene (GRIN2B) [PMID 21861710] A Novel DRD2 Single-Nucleotide Polymorphism Associated with Schizophrenia Predicts Age of Onset: HapMap Tag-Single-Nucleotide Polymorphism Analysis [PMID 22745721] Cannabis-Dependence Risk Relates to Synergism between Neuroticism and Proenkephalin SNPs Associated with Amygdala Gene Expression: Case-Control Study [PMID 16848906] Genetic polymorphisms in monoamine neurotransmitter systems show only weak association with acute post-surgical pain in humans. [PMID 16867246] Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients. [PMID 17135598] No evidence for a major role of polymorphisms during bupropion treatment. [PMID 18077373] Polymorphisms in human dopamine D2 receptor gene affect gene expression, splicing, and neuronal activity during working memory. [PMID 18332877] Family-based association testing strongly implicates DRD2 as a risk gene for schizophrenia in Han Chinese from Taiwan. [PMID 18563706] The impact of genetic variation in DRD2 and SLC6A3 on smoking cessation in a cohort of participants 1 year after enrollment in a lung cancer screening study. [PMID 18690117] Gene and gene by sex associations with initial sensitivity to nicotine in nonsmokers. [PMID 18698231] Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues. [PMID 18929622] Dopamine 2 receptor C957T and catechol-o-methyltransferase Val158Met polymorphisms are associated with treatment response in electroconvulsive therapy. [PMID 19065655] Dopamine D2 receptor polymorphisms and adenoma recurrence in the Polyp Prevention Trial. [PMID 19158809] Case-control association study of 59 candidate genes reveals the DRD2 SNP (C957T) as the only susceptibility factor for schizophrenia in the Bulgarian population. [PMID 19197363] A genome-wide investigation of SNPs and CNVs in schizophrenia. [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 19393722] Genetic contributions to avoidance-based decisions: striatal D2 receptor polymorphisms. [PMID 19470168] NPAS2 and PER2 are linked to risk factors of the metabolic syndrome. [PMID 19590515] Association between dopaminergic genes (SLC6A3 and DRD2) and stuttering among Han Chinese. [PMID 19693267] Financial and psychological risk attitudes associated with two single nucleotide polymorphisms in the nicotine receptor (CHRNA4) gene. [PMID 19911060] Persistence criteria for susceptibility genes for schizophrenia: a discussion from an evolutionary viewpoint. [PMID 19913597] An association study of DRD2 gene polymorphisms with schizophrenia in a Chinese Han population. [PMID 20179754] Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance. [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 20205808] Association between dopaminergic polymorphisms and borderline personality traits among at-risk young adults and psychiatric inpatients. [PMID 20567893] Association between polymorphisms of the dopamine receptor D2 and catechol-o-methyl transferase genes and cognitive function. [PMID 20615259] A polymorphism in the dysbindin gene (DTNBP1) associated with multiple psychiatric disorders including schizophrenia. [PMID 21130611] Evidence for the modality independence of the genetic epistasis between the dopaminergic and cholinergic system on working memory capacity. [PMID 21172166] Pharmacogenetics of antidepressant response. [PMID 21508242] Dopaminergic genes predict individual differences in susceptibility to confirmation bias. [PMID 22382052] A DRD2 and ANKK1 haplotype is associated with nicotine dependence. [PMID 22487365] C957T polymorphism of the dopamine D2 receptor gene is associated with motor learning and heart rate. [PMID 22574669] Dopamine receptors D1 and D2 are related to observed maternal behavior. [PMID 22582185] DRD2 C957T and TaqIA Genotyping Reveals Gender Effects and Unique Low-Risk and High-Risk Genotypes in Alcohol Dependence. [PMID 22937132] The Protein Kinase KIS Impacts Gene Expression during Development and Fear Conditioning in Adult Mice [PMID 24018103] Association study of the vesicular monoamine transporter gene SLC18A2 with tardive dyskinesia [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 22579533] Binge eating disorder and the dopamine D2 receptor: genotypes and sub-phenotypes. [PMID 22939506] Aging magnifies the effects of dopamine transporter and D2 receptor genes on backward serial memory. [PMID 22947540] The dopamine D2 receptor gene DRD2 and the nicotinic acetylcholine receptor gene CHRNA4 interact on striatal gray matter volume: evidence from a genetic imaging study. [PMID 23376770] The genetic impact (C957T-DRD2) on inhibitory control is magnified by aging. [PMID 25647695] Modulation of nicotine effects on selective attention by DRD2 and CHRNA4 gene polymorphisms [PMID 26307064] DRD2 and DRD4 genes related to cognitive deficits in HIV-infected adults who abuse alcohol [PMID 26370377] Recurrent miscarriage is associated with the dopamine receptor (DRD2) genotype [PMID 26445370] Genetic Effects on Longitudinal Changes from Healthy to Adverse Weight and Metabolic Status – The HUNT Study

Mechanism:

• Decreased dopamine signaling (AA) [R].
• Lower DRD2 (A) [R].
• Low striatal DRD2 availability (GG) [R]
• High extrastriatal DRD2  (GG)[R]

The Minor "A" allele is associated with:

• Needing higher dose of methadone [R].
• A longer time to reach the maximum methadone dose (P=0.025) [R].
• Better response to treatment with methadone than patients with GG genotype (AA) (AG) [R]
• Tend to be better NoGo learners (AA) [R]. NoGo is a game measuring the ability to hold off on the action of button pushing [R]. Higher dopamine in the basal ganglia helps people learn to repeat rewarding behaviors, while lower dopamine leads to better learning from bad experiences. In a game where X usually yields more points than Y, people with boosted dopamine levels learn to choose X. People with decreased dopamine levels learn to avoid Y [R]. In non-medicated test subjects, genetic variations that influence dopamine signaling in the basal ganglia also impact so-called Go (choose X) and NoGo learning (avoid Y) [R].
• Combination of the A allele of the DRD2 gene and the Met allele of the COMT gene predicts more severe depression. Patients with this genotype do not have the same response to patients with GG to ECT and do not achieve remission as often as those with the GG genotype [R]  
• The effects of nicotine to newly exposed individuals revealed a greater feeling of perception, anger, and reduced fatigue (AA) [R]  
• Higher risk of schizophrenia (A) [R]  [R]

The Major "G" allele is associated with:

• 1.42X higher risk of schizophrenia (G) (p<0.00005) [R]  .
• 1.6X increased risk for Schizophrenia (GG) (p<0.00005) [R] .
• PTSD (G) (p = 0.021) [R] .
• Decreased general cognitive ability (p=0.003) (GG) [R]
• Increased risk of developing a stutter (G) (n=chinese population) [R]
• 3.3 times more likely to have a dependence to nicotine (GG along with a copy of the Taql A1-allele) This combination of accounts for 13% of the susceptibility to nicotine addiction in our population [R]  
• Faster learning (GG) [R]  
• Alcohol dependence  (GG) [R]
• Better with better backward serial recall, which includes retrieval demands (GG) [R]
• More efficient in inhibiting unwanted action tendencies (GG)  [R]

This SNP is associated with (unknown alleles):

• Maternal infant-directed vocalizing  [R]
• Binge eating disorders [R]
• Cognitive flexibility in patients with HIV who abuse alcohol  [R]
• Recurrent miscarriages (Odds ratio=2.37) [R]
• Weight gain  [R]