title: Clinical response to antipsychotic drug treatment: association study of polymorphisms in six candidate genes.
abstract: Pharmacogenetic studies have demonstrated significant associations between several candidate genes (DRD2, DRD3, 5HTR2A and 5HTR2C, COMT and MTHFR) and antipsychotic drug response. The present study investigates the effect of nine polymorphisms in these genes for an association with antipsychotic treatment response. 329 Caucasian patients with a non-affective psychotic disorder using antipsychotics were included. All patients participated in the longitudinal GROUP-study in The Netherlands. We genotyped 9 SNPs in 6 candidate genes (DRD2: TaqI_A, -141C; DRD3: Ser9Gly; HTR2A: 102-T/C, His452Tyr; HTR2C: Cys23Ser; COMT: Val158Met; MTHFR: 677-C/T) using standard protocols. Polymorphisms were based on previous studies showing associations with positive symptoms treatment response. The Clinical Global Impression - Improvement (CGI-I) scale was used to assess improvement in positive psychotic symptoms since the start of current antipsychotic treatment. Ordinal regression was used for association analyses. Ninety percent of the patients used second generation antipsychotics, with olanzapine (28%) and risperidone (29%) being the most prescribed drugs. Ser9Gly of the dopamine D3 receptor gene (P value 0.034) and 677-C/T of MTHFR (P value 0.019) were tested statistically significant. Gly-carriers and T-carriers, respectively, showed more clinical improvement on the CGI-I. The other polymorphisms did not show a statistically significant association (P values>0.10). In conclusion, we replicated two out of nine of the previously reported associations between polymorphisms and treatment response. The direction and magnitude of the associations presented here in DRD3 (Ser9Gly) and MTHFR (677-C/T) are in line with previous association studies in Caucasian patients. These polymorphisms may be of value for predicting clinical response.
authors.affiliation: Department of Psychiatry University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. j.vehof@umcg.nl
authors.forename: Jelle
authors.initials: J
authors.lastname: Vehof
authors.forename: Huibert
authors.initials: H
authors.lastname: Burger
authors.forename: Bob
authors.initials: B
authors.lastname: Wilffert
authors.forename: Asmar
authors.initials: A
authors.lastname: Al Hadithy
authors.forename: Behrooz Z
authors.initials: BZ
authors.lastname: Alizadeh
authors.forename: Harold
authors.initials: H
authors.lastname: Snieder
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods* / Q000706:statistics & numerical data; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D014150:Antipsychotic Agents; D050637:Receptors, Dopamine D3; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)