From SNPedia
| Geno
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Mag
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Summary
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| (C;C)
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0
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| (C;T)
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2
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bupropion ineffective
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| (T;T)
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4
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A1/A1 bupropion ineffective, diminished pleasure response; 2.4x increased risk for adenoma recurrence
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| ? | (C;C) (C;T) (T;T) | 28 |
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, 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.[PMID 19065655]
[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.
spittoon 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
| OMIM | 608774 |
| Desc | ANKYRIN REPEAT AND KINASE DOMAIN CONTAINING 1; ANKK1 |
| Variant | |
| Related | also |
[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
| PharmGKB | PA165291720 |
| Name | Taq1A (32806C>T) |
| Annotation | Risk or phenotype-associated genotype: T. Phenotype: The A1 allele is associated with 24 (69%) of 35 alcoholics, but it associated with only 7 (20%) of 35 nonalcoholics. The absence of the A1 allele is associated with 28 (80%) of 35 nonalcoholics and with only 11 (31%) of 35 alcoholics. Study size: 35 alcoholics and 35 nonalcoholics. Study population: 46 whites; 24 blacks |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:1969501 |
| Drugs | ethanol |
| Diseases | Alcoholism |
| Curation Level | Curated |
[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
| PharmGKB | PA162171873 |
| Name | DRD2 Taq1A |
| Annotation | This variant (A2/A2 genotype) is associated with improved response to bupropion efficacy for smoking cessation. |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:18058343 |
| Drugs | bupropion |
| Diseases | Tobacco Use Disorder |
| Curation Level | Curated |
| PharmGKB | PA162356250 |
| Name | DRD2: TaqIA |
| Annotation | This SNP is significant predictor of treatment response to risperidone in first-episode schizophrenia. |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:18855532 |
| Drugs | risperidone |
| Diseases | Schizophrenia |
| Curation Level | Curated |
| PharmGKB | PA162370416 |
| Name | DRD2:TaqIA allele |
| Annotation | In blood oxygen level-dependent functional magnetic resonance imaging studies, obese college-aged women and adolescent girls showed a blunted striatal response to chocolate milkshake tasting (vs. tasting of a tasteless solution) when compared to lean women and girls, and the genotype at this SNP affected the extent of this response. This SNP is known as the TaqIA allele of DRD2 even though it is more than 10 KB downstream from the gene boundary. |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:18927395 |
| Drugs | |
| Diseases | Obesity |
| Curation Level | Curated |
| PharmGKB | PA165108050 |
| Name | DRD2:Taq1A A1 |
| Annotation | Risk or phenotype-associated allele: T. Phenotype: Carriers of one or two copies of the T allele of this variant (also known as Taq1A A1) were at higher risk of developing hyperprolactinemia than those with two copies of the C allele (also known as Taq1A A2). This variant is a SNP located about 9.5 kb downstream of the DRD2 coding region, and results in a Glu (C allele) to Lys (T allele) amino acid substitution in the ANKK1 protein. Study size: 90. Study population/ethnicity: 7-17-year-old patients chronically treated with risperidone; non-Hispanic Caucasians. Significance metric(s): OR = 3.1; p < 0.05. Type of association: CO. |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:19339912 |
| Drugs | risperidone |
| Diseases | Hyperprolactinemia |
| Curation Level | Curated |
| PharmGKB | PA165291714 |
| Name | Taq1A (32806C>T) |
| Annotation | Risk or phenotype-associated genotype: T/T. Phenotype: Patients with one or two A1 alleles (T/T) had a greater risk of significant side effects, particularly if they were male. Study size: 116. Study population: Caucasians. |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:18086475 |
| Drugs | |
| Diseases | |
| Curation Level | Curated |
| PharmGKB | PA165291715 |
| Name | Taq1A (32806C>T) |
| Annotation | Risk or phenotype-associated genotype: C/C. Phenotype: A meta-analysis showed that compared to tardive dyskinesia (TD)-negative patients, TD-positive patients had a higher A2 allele frequency (P = 0.003), with an effect-size of 1.30 (95% CI: 1.09-1.55), and higher A2/A2 genotype frequency (P = 0.001), with an effect-size of 1.50 (95% CI: 1.17-1.92). Study size: 1256 schizophrenia patients. |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:17767146 |
| Drugs | |
| Diseases | tardive dyskinesia |
| Curation Level | Curated |
| PharmGKB | PA165291718 |
| Name | Taq1A (32806C>T) |
| Annotation | Phenotype: This study found no association between the Taq1A polymorphism and response to nicotine replacement therapy. |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:19273465 |
| Drugs | |
| Diseases | Tobacco Use Disorder |
| Curation Level | Curated |
| PharmGKB | PA165291719 |
| Name | Taq1A (32806C>T) |
| Annotation | Risk or phenotype-associated genotype: T. Phenotype: Compared to women who carry both A2 (CC) alleles, women with at least one A1 (T) allele were more likely to report having stopped taking bupropion due to medication side effects (odds ratio (OR)=1.91, 95% confidence interval (CI)=1.01-3.60; P<0.04) and at 12 months were somewhat more likely to report smoking (OR=0.76, 95% CI=0.56-1.03; P<0.076). Significant associations or trends were not observed in men. Study size: 451 participants. Study population: Caucasian. |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:15492764 |
| Drugs | bupropion |
| Diseases | Tobacco Use Disorder |
| Curation Level | Curated |
| PharmGKB | PA165291721 |
| Name | Taq1A (32806C>T) |
| Annotation | Risk or phenotype-associated genotype: T. Phenotype: This meta-analysis included 44 studies with 9,382 participants. For all studies combined, when we assumed the dominant model of gene action (A1A1 + A1A2 vs. A2A2), a small but significant association of alcohol dependency with being homozygote or heterozygote for the A1 allele was detected. The odds ratio was 1.38 (95 percent confidence interval (CI): 1.20, 1.58) when random effects were used. Study size: 5,273 cases and 3,995 controls. |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:17989061 |
| Drugs | ethanol |
| Diseases | Alcoholism |
| Curation Level | Curated |
| PharmGKB | PA165291618 |
| Name | TaqIA |
| Annotation | Risk or phenotype-associated allele: T (A1). Phenotype: In a smoking cessation study the TaqIA SNP was significantly associated with being abstinent at 1 year (P = 0.01). Participants who carried at least one minor allele (A1) were less likely to quit compared to A2A2 homozygous (Odds Ratio: 0.47, 95% CI: 0.24-0.94). Study size: 881. metric(s): OR =0.47, 95% CI: 0.24-0.94. |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:18563706 |
| Drugs | |
| Diseases | Tobacco Use Disorder |
| Curation Level | Curated |
| PharmGKB | PA165291713 |
| Name | Taq1A (32806C>T) |
| Annotation | Risk or phenotype-associated allele: T. Phenotype: In the combined medication group patients with the A1 (T) allele had 40% higher prolactin levels than patients without this allele. Study size: 144 schizophrenic patients. Study population: White patients. |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:15286066 |
| Drugs | clozapine, olanzapine, risperidone |
| Diseases | Hyperprolactinemia |
| Curation Level | Curated |
| PharmGKB | PA165291717 |
| Name | Taq1A (32806C>T) |
| Annotation | Risk associated genotype: C/C. Phenotype: In a randomized controlled trial investigating the short-term effectiveness of the nicotine patch, after 1 week of the trial the patch was more effective for smokers with CT/TT genotype (OR 2.80, 95% CI 1.70-4.61) than with CC (OR 1.41, 0.94-2.12; P for difference in ORs 0.04). Study size: 1532. |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:15077009 |
| Drugs | |
| Diseases | Tobacco Use Disorder |
| Curation Level | Curated |
| PharmGKB | PA165291688 |
| Name | TaqIA |
| Annotation | Phenotype: In this case-control study the polymorphisms -141C Ins/Del (rs1799732); C957T (rs6277); A1385G (rs6276); and TaqIA (rs1800497) were genotyped. The haplotypes I-C-G-A2 and I-C-A-A1 occurred with a higher frequency in alcoholics [P=0.026, odds ratio (OR): 1.340; P=0.010, OR: 1.521, respectively]. Study size: 360 alcoholics and 368 controls. Study population:Caucasian individuals of German origin. |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:19603545 |
| Drugs | ethanol |
| Diseases | Alcoholism |
| Curation Level | Curated |
| PharmGKB | PA165291677 |
| Name | TaqIA (C/T) |
| Annotation | Phenotype: Compared with patients who had the A2/A2 (C/C) genotype, the positive and negative syndrome scale (PANSS) positive scores of A1/A1 (T/T) patients were 3.71 lower (p = 0.01) and of A1/A2 patients were 1.36 lower (p = 0.03) after 4-week aripiprazole treatment. These results suggest that A1 carriers are associated with superior therapeutic response on positive symptoms. Study size: 128 schizophrenic patients. Study population: Chinese. |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:18926547 |
| Drugs | aripiprazole |
| Diseases | Schizophrenia |
| Curation Level | Curated |
| PharmGKB | PA165291712 |
| Name | Taq1A (32806C>T) |
| Annotation | Risk or phenotype-associated allele: T. Phenotype: In schizophrenic patients treated with nemonapride, the delta prolactin at 1 and 3 weeks was significantly (P<0.05) higher in female patients with the A1 allele than in males with or with no A1 allele. The delta prolactin at 3 weeks was also significantly (P<0.05) higher in the female patients with the A1 allele than in those with no A1 allele. Study size: 25 schizophrenic inpatients. Study population: Japanese. |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:10823405 |
| Drugs | nemonapride |
| Diseases | Hyperprolactinemia |
| Curation Level | Curated |
| PharmGKB | PA165291716 |
| Name | Taq1A (32806C>T) |
| Annotation | Risk or phenotype-associated genotype: C/C. Phenotype: This meta-analysis suggests multiple genetic influences on tardive dyskinesia, including the Taq1A SNP. For Taq1A using the A1 allele as reference category, the study showed a risk-increasing effect for the A2 variant (OR=1.30, 95% CI: 1.03-1.65, P=0.026), and for A2-A2 homozygotes using A1-A1 as reference category (OR=1.80, 95% CI: 1.03-3.15, P=0.037). |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:18180754 |
| Drugs | |
| Diseases | tardive dyskinesia |
| Curation Level | Curated |
| PharmGKB | PA165374659 |
| Name | TaqIA |
| Annotation | Risk or phenotype-associated allele: T. Phenotype: The T allele was associated with weight gain of at least 7% in schizophrenia patients treatment with clozapine or olanzapine. Study size: 206. Study population/ethnicity: European american; German; Schizophrenia. Significance metric(s): OR = 2.18 (CI: 1.00-4.75). Type of association: PD. |
| Gene | ANKK1 |
| Featue | |
| Evidence | PubMed ID:20714340 |
| Drugs | clozapine, olanzapine |
| Diseases | Weight gain |
| Curation Level | Curated |
[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
