Objective: Schizophrenic patients treated with atypical antipsychotics (AAPs) often develop excessive body weight gain (BWG), which may lead to further morbidity and poor treatment compliance. This study examined whether genetic variants in the dopamine receptor D2 (DRD2) gene may be associated with body weight change after AAP treatment.
Methods: The study included 479 schizophrenic patients treated with clozapine (n=239), olanzapine (n=70) or risperidone (n=170) for an average of 48.2+/-27.8 months. BWG was defined as an increase of more than 7% of the baseline body weight during AAP treatment. Thirteen common single nucleotide polymorphisms of the DRD2 gene were chosen as tagging single nucleotide polymorphisms.
Results: In single-marker-based analysis, the DRD2 rs4436578-C homozygous genotype was found to be associated with a significantly increased risk of BWG [P=0.001, adjusted odds ratio=3.36 (95% confidence interval=1.62 - 7.00)]. In addition, haplotype analysis further showed that the rs4436578-C-allele-related haplotype was more frequent in those patients with BWG than those without (P=0.01 - 0.00019).
Conclusion: Our findings confirm the importance of genetic factors in body weight change induced by long-term AAP treatment in patients with schizophrenia and indicate a role of DRD2 in body weight regulation during long-term AAP treatment.