title: The influence of 5-HT(2C) and MDR1 genetic polymorphisms on antipsychotic-induced weight gain in female schizophrenic patients.
abstract: We investigated the relationships between functional genetic variants of the 5-HT(2C) receptor and multidrug-resistant protein (MDR1), coding for P-glycoprotein, and second generation antipsychotic (SDA)-induced weight gain among 108 female schizophrenic patients treated with olanzapine or risperidone for up to 4 months. No significant differences in -759C/T allelic and genotype variants of 5-HT(2C) were found between patients who gained more than 7% of their initial weight compared with those who gained less. Haplotype-based analysis of two MDR1 loci, exon 21 G2677T and exon 26 C3435T, revealed a slightly lower representation of the G2677/C3435 haplotype in the >or=7% group. In the subgroup of patients treated with risperidone, we found borderline overrepresentation of 2677T, significant overrepresentation of 3435T variant and borderline overrepresentation of 2677T/3435T haplotype the >or=7% group, whereas G2677/C3435 haplotype was found to be less represented in the >or=7% group. Our data indicate a nonsignificant role of 759C/T 5-HT(2C) in SDA-induced weight gain, and a stronger influence of the MDR1 G2677T and C3435T polymorphisms on risperidone-induced weight gain in female schizophrenic patients. 3435T and 2677T MDR1 variants, both associated with lower P-gp function, might predispose to higher risperidone accessibility to the brain that would lead to stronger effects, including weight gain.
authors: Department of Psychiatry, Zagreb University Hospital Centre, Kispaticeva 12 10000 Zagreb, Croatia. mrojnic@gmail.com
authors: Martina Rojnic
authors: MR
authors: Kuzman
authors: Vesna
authors: V
authors: Medved
authors: Nada
authors: N
authors: Bozina
authors: Ljubomir
authors: L
authors: Hotujac
authors: Ivica
authors: I
authors: Sain
authors: Hrvoje
authors: H
authors: Bilusic
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D019450:Genes, MDR / Q000187:drug effects / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000187:drug effects / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D009765:Obesity / Q000139:chemically induced; D000077152:Olanzapine; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects / Q000235:genetics*; D018967:Risperidone / Q000009:adverse effects* / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014150:Antipsychotic Agents; D044405:Receptor, Serotonin, 5-HT2C; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine