The influence of 5-HT2C and MDR1 genetic polymorphisms on antipsychotic-induced weight gain in female schizophrenic patients

• Published in: Psychiatry research Vol. 160; no. 3; pp. 308 - 315
• Main Authors: Kuzman, Martina Rojnic, Medved, Vesna, Bozina, Nada, Hotujac, Ljubomir, Sain, Ivica, Bilusic, Hrvoje
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier 30.09.2008
• Subjects: Biological and medical sciences; Drug toxicity and drugs side effects treatment; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Pharmacology. Drug treatments; Psychiatry; MDR1; Olanzapine; Genetic polymorphism; Schizophrenia; Risperidone; 5-HT 2C; Weight gain; Atypical antipsychotic; Neuroleptic; Psychotropic; Toxicity; Pharmacotherapy; Serotonine receptor; Genetic determinism; Psychosis; Genetics; Woman; 5-HT2C serotonin receptor; Benzisoxazole derivatives; Human; Dopamine antagonist; Serotonin antagonist; Genetic variant; Thienobenzodiazepine derivatives; D2 Dopamine receptor; Treatment; MDR-1 gene; 5-HT2C; Polymorphism
• ISSN: 0165-1781; 1872-7123
• DOI: 10.1016/j.psychres.2007.06.006

Abstract We investigated the relationships between functional genetic variants of the 5-HT2C 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-HT2C 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 ≥ 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 ≥ 7% group, whereas G2677/C3435 haplotype was found to be less represented in the ≥ 7% group. Our data indicate a nonsignificant role of 759C/T 5-HT2C 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.