Genetics/DRD2

The DRD2 gene codes for the dopamine receptor D2. This polymorphic gene is located on chromosome 11. Point mutations in and near the coding region of the DRD2 gene which have a major impact on personality.

Basal personality endophenotypes
Four basal personality endophenotypes are associated with polymorphisms in the ANKK1 gene and D2 receptor response to dopamine: calm, anxious, impulsive, and dissocial.

Personality phenotypes
A number of distinct personality phenotypes have been associated with polymorphisms in and near the DRD2 gene.

The –141C ins/del polymorphism
The –141C ins/del polymorphism is located in the promoter region of the DRD2 gene 141 base pairs upstream of the coding region. This polymorphism has been associated with a detached personality type. The –141C ins/del polymorphism may be associated with a blunted expression of DRD2 receptors in response to dopamine.

The C957T polymorphism
The C957T polymorphism is a synonymous mutation located within the coding region of the DRD2 gene. This mutation affects the conformation and stability of DRD2 messenger RNA. The C957T polymorphism might not influence the intensity of the initial expression of DRD2 receptors in response to dopamine. However, it may influence the duration of that response. In any event, the T allele appears to be associated with decreased D2 receptor expression compared to the C allele. The C957C genotype is associated with a reward-related impulsivity endophenotype in response to acute psychosocial stress. The C957C genotype is also associated with schizophrenia.

The TaqI-A polymorphism
Although the TaqI-A polymorphism is traditionally associated with the DRD2 gene itself, it is actually a single nucleotide polymorphism (Glu713Lys) located 9.4 Kb downstream of the DRD2 gene in the coding region of the ANKK1 gene. This gene controls the synthesis of dopamine. Phenotypic expression of the TaqI-A polymorphism differs according to gender. Results of studies of this polymorphism involving males should be interpreted with caution when being applied to females.

A1 allele
The TaqI-A A1 allele is associated with a reduced expression of D2 receptors, an increased susceptibility to Neuroleptic malignant syndrome  and posttraumatic stress disorder. The C957T CC genotype and the TaqI-A A1 allele are epistatically associated with dissocial personality disorder among alcoholics.

A2 allele
The TaqI-A A2 allele is associated with smoking.

Height and Body Mass
In addition to the three point mutations discussed above, two additional single nucleotide polymorphisms within the DRD2 gene have been associated with height and body mass. These two mutations may reduce the binding affinity of the D2 receptors. L-tyrosine, a metabolic precursor to dopamine has been proposed as a treatment for obesity.

Avoidant personality disorder
A detached personality is associated with the –141C ins/del polymorphism in the promoter region of the DRD2 gene, and avoidant attachment is associated with a polymorphism of the 5HT2A serotonin receptor gene. Avoidant personality disorder has also been associated with Taq A1 allele.

Also see
DSM-5 Personality Disorders