Rs1800497

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.

Reduced response to errors and increased addictive behavior

It 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).

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. 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.

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.

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.

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.

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.

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).

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

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Avoidance of Errors

Postoperative Nausea and Vomiting

A variant in ANKK1 modulates acute subjective effects of cocaine: a preliminary study.

Living in the moment: Effects of time perspective and emotional valence of episodic thinking on delay discounting.

Single-nucleotide polymorphisms of the dopamine d2 receptor increase inflammation and fibrosis in human renal proximal tubule cells.

Polymorphisms in the dopamine receptor 2 gene region influence improvements during working memory training in children and adolescents.