title: Association between 5-HT2A, TPH1 and GNB3 genotypes and response to typical neuroleptics: a serotonergic approach.
abstract: BACKGROUND
  Schizophrenia is a common psychiatric disease affecting about 1% of population. One major problem in the treatment is finding the right the drug for the right patients. However, pharmacogenetic results in psychiatry can seldom be replicated.
  
  
  METHODS
  We selected three candidate genes associated with serotonergic neurotransmission for the study: serotonin 2A (5-HT2A) receptor gene, tryptophan hydroxylase 1 (TPH1) gene, and G-protein beta-3 subunit (GNB3) gene. We recruited 94 schizophrenia patients representing extremes in treatment response to typical neuroleptics: 43 were good responders and 51 were poor responders. The control group consisted of 392 healthy blood donors.
  
  
  RESULTS
  We do, in part, replicate the association between 5-HT2A T102C polymorphism and response to typical neuroleptics. In female patients, C/C genotype was significantly more common in non-responders than in responders [OR = 6.04 (95% Cl 1.67-21.93), p = 0.005] or in the control population [OR = 4.16 (95% CI 1.46-11.84), p = 0.005]. TPH1 A779C C/A genotype was inversely associated with good treatment response when compared with non-responders [OR = 0.59 (95% Cl 0.36-0.98), p = 0.030] or with the controls [OR = 0.44 (95% CI 0.23-0.86, p = 0.016], and GNB3 C825T C/T genotype showed a trend-like positive association among the male patients with a good response compared with non-responders [OR = 3.48 (95% Cl 0.92-13.25), p = 0.061], and a clearer association when compared with the controls [OR = 4.95 (95% CI 1.56-15.70), p = 0.004].
  
  
  CONCLUSIONS
  More findings on the consequences of functional polymorphisms for the role of serotonin in the development of brain and serotonergic neurotransmission are needed before more detailed hypotheses regarding susceptibility and outcome in schizophrenia can be formulated. The present results may highlight some of the biological mechanisms in different courses of schizophrenia between men and women.
authors.affiliation: University of Tampere, Medical School, University of Tampere, Finland. samia@koti.soon.fi <samia@koti.soon.fi>
authors.forename: Sami
authors.initials: S
authors.lastname: Anttila
authors.forename: Olli
authors.initials: O
authors.lastname: Kampman
authors.forename: Ari
authors.initials: A
authors.lastname: Illi
authors.forename: Riikka
authors.initials: R
authors.lastname: Rontu
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: Esa
authors.initials: E
authors.lastname: Leinonen
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D016022:Case-Control Studies; D004351:Drug Resistance; D005260:Female; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011985:Receptors, Serotonin / Q000235:genetics* / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D012701:Serotonin / Q000502:physiology; D012737:Sex Factors; D016896:Treatment Outcome; D014365:Tryptophan Hydroxylase / Q000235:genetics* / Q000502:physiology
chemical_list: D014150:Antipsychotic Agents; C454420:G-protein beta3 subunit; D011985:Receptors, Serotonin; C078730:serotonin 5 receptor; D012701:Serotonin; C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase; D020962:Heterotrimeric GTP-Binding Proteins