Association of htr2a polymorphisms with risperidone efficacy in chinese han schizophrenia patients

Abstract

Objectives: The 5-HT2A receptor is one of the most important serotonin receptors, serving as amajor target for risperidone. Rs6311 and rs6313 polymorphisms in the HTR2A gene have beenreported to be associated with response to risperidone treatment; however, many previousstudies have yielded conflicting results. To confirm the importance of these polymorphisms inrisperidone treatment and provide more evidence for the routine use of these pharmacogeneticbiomarkers in clinical practice, we carried out an association analysis of rs6311 and rs6313polymorphisms with risperidone efficacy in Chinese Han patients with schizophrenia.Methods: Two independent cohorts of unrelated subjects were recruited from Henan andShanghai (95 and 113 subjects, respectively). After 4- or 8-week risperidone monotherapy,the rs6311 and rs6313 polymorphisms of these subjects were genotyped with direct DNAsequencing. Clinical improvement was measured by the reduction of the PANSS scores (includingthe total and subscale scores). UNIANOVA and case-control study was used to evaluate theeffects of rs6311 and rs6313 polymorphisms on the therapeutic efficacy of risperidone.Results: As in previous studies, the rs6311G allele was found in complete linkage disequilibriumwith the rs6313C allele. However, neither the rs6311 nor the rs6313 polymorphism significantlyinfluenced clinical improvement during risperidone treatment. Neither the allele nor thegenotype frequencies were significantly different between responder and non-respondersubgroups.Conclusions: No significant association between HTR2A polymorphisms (rs6313 and rs6311)and risperidone efficacy was found in the present study. The relative large sample size and twoindependent cohorts of subjects in the present study enhance the reliability of our findings.