C957T

The C957T gene polymorphism is a synonymous mutation located within the 957th base pair of the DRD2 gene. This base pair is located in exon 7. Most synonymous mutations are silent. However, the C957T mutation is an exception to this rule. While the 957C allele codes for the same polypeptide as the 957T allele, the conformation of 957T messenger RNA differs from the conformation of 957C messenger RNA. 957T messenger RNA is less stable and more prone to degradation. As a result, dopamine D2 receptor expression is decreased among individuals who carry the 957T allele compared to individuals who carry the 957C allele.[1]

Behaviours associated with the C/C genotype of the C957T polymorphism

Given that the C/C genotype has been associated with dissocial personality disorder one may infer that this genotype may also be associated with all four DSM-IV defined cluster B personality disorders. This hypothesis, however, has not been tested.

Rapid screening of the C957T and the TaqIA polymorphisms

Given the importance of the C957T and TaqIA polymorphisms for the diagnosis and treatment of psychological disorder, a rapid screening protocol for these genes has been developed.[13] Since the DRD2 1101A allele nulls the effects of the 957T allele,[14] screens for the 957C allele which ignore the 1101A allele can sometimes lead to false negatives.

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References
  1. Hirvonen, M; Laakso, A; Någren, K; Rinne, J O; Pohjalainen, T; Hietala, J (2004). "C957T polymorphism of the dopamine D2 receptor (DRD2) gene affects striatal DRD2 availability in vivo". Molecular Psychiatry. 9 (12): 1060–1061. doi:10.1038/sj.mp.4001561. ISSN 1359-4184. PMID 15278099.
  2. Lawford, Bruce R. (2005). "The C/C genotype of the C957T polymorphism of the dopamine D2 receptor is associated with schizophrenia". Schizophrenia Research. 73 (1): 31–37. doi:10.1016/j.schres.2004.08.020. PMID 15567074.
  3. Hänninen, Kari (2006). "Association between the C957T polymorphism of the dopamine D2 receptor gene and schizophrenia". Neuroscience Letters. 407 (3): 195–198. doi:10.1016/j.neulet.2006.08.041. PMID 16973280.
  4. Xu, H; Kellendonk, CB; Simpson, EH; Keilp, JG; Bruder, GE; Polan, HJ; Kandel, ER; Gilliam, TC (2007). "DRD2 C957T polymorphism interacts with the COMT Val158Met polymorphism in human working memory ability". Schizophrenia Research. 90 (1–3): 104–107. doi:10.1016/j.schres.2006.10.001. PMID 17113268.
  5. Jacobsen LK, Pugh KR, Mencl WE, Gelernter J (2006). "C957T polymorphism of the dopamine D2 receptor gene modulates the effect of nicotine on working memory performance and cortical processing efficiency". Psychopharmacology. 188 (4): 530–40. doi:10.1007/s00213-006-0469-1. PMID 16896957.
  6. White MJ, Lawford BR, Morris CP, Young RM (2009). "Interaction between DRD2 C957T polymorphism and an acute psychosocial stressor on reward-related behavioral impulsivity" (PDF). Behav. Genet. 39 (3): 285–95. doi:10.1007/s10519-008-9255-7. PMID 19148742.
  7. Eny, Karen M.; Corey, Paul N.; El-Sohemy, Ahmed (2009). "Dopamine D2 Receptor Genotype (C957T) and Habitual Consumption of Sugars in a Free-Living Population of Men and Women". Journal of Nutrigenetics and Nutrigenomics. 2 (4–5): 235–242. doi:10.1159/000276991. ISSN 1661-6758. PMID 20357494.
  8. Cambridge Journals Online - Abstract
  9. Mo, GH; Lai, IC; Wang, YC; Chen, JY; Lin, CY; Chen, TT; Chen, ML; Liou, YJ; Liao, DL; Bai, YM; Lin, CC (2007). "Support for an association of the C939T polymorphism in the human DRD2 gene with tardive dyskinesia in schizophrenia". Schizophrenia Research. 97 (1–3): 302–304. doi:10.1016/j.schres.2007.06.026. PMID 17669630.
  10. Huertas, E. (2010). "The D2 dopamine receptor gene variant C957T affects human fear conditioning and aversive priming". Genes, Brain and Behavior. 9 (1): 103–109. doi:10.1111/j.1601-183X.2009.00543.x. PMID 19900188.
  11. Ponce, G.; Hoenicka, J.; Jiménez-Arriero, M. A.; Rodríguez-Jiménez, R.; Aragüés, M.; Martín-Suñé, N.; Huertas, E.; Palomo, T. (2018). "DRD2 and ANKK1 genotype in alcohol-dependent patients with psychopathic traits: Association and interaction study". British Journal of Psychiatry. 193 (2): 121–125. doi:10.1192/bjp.bp.107.041582. ISSN 0007-1250. PMID 18669994.
  12. Voisey, Joanne (2009). "The DRD2 gene 957C>T polymorphism is associated with Posttraumatic Stress Disorder in war veterans" (PDF). Depression and Anxiety. 26 (1): 28–33. doi:10.1002/da.20517. PMID 18833581.>T polymorphism is associated with Posttraumatic Stress Disorder in war veterans - Voisey - 2008 - Depression and Anxiety - Wiley Online Library]
  13. Stefan P, Moritz E, Alexander W, Weber M, Norbert D, Annette W, Thomas F, Andreas P (2009). "Development of a high-throughput method for screening the dopamine D2 (DRD2) receptor gene polymorphisms based on the LightCycler system". Clinical Laboratory. 55 (9–10): 353–8. PMID 20099571.
  14. Duan, J. (2003). "Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor". Human Molecular Genetics. 12 (3): 205–216. doi:10.1093/hmg/ddg055. ISSN 1460-2083. PMID 12554675.
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