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Huo R.,Shanghai JiaoTong University | Huo R.,Shanghai Genomepilot Institutes | Tang K.,Shanghai JiaoTong University | Tang K.,Shanghai Genomepilot Institutes | And 21 more authors.
PLoS ONE | Year: 2012

Background: CYP2E1 is a member of the cytochrome P450 superfamily, which is involved in the metabolism and activation of both endobiotics and xenobiotics. The genetic polymorphisms of CYP2E1 gene (Chromosome 10q26.3, Accession Number NC_000010.10) are reported to be related to the development of several mental diseases and to be involved in the clinical efficacy of some psychiatric medications. We investigated the possible association of CYP2E1 polymorphisms with susceptibility to schizophrenia in the Chinese Han Population as well as the relationship with response to risperidone in schizophrenia patients. Methods: In a case-control study, we identified 11 polymorphisms in the 5' flanking region of CYP2E1 in 228 schizophrenia patients and 384 healthy controls of Chinese Han origin. From among the cases, we chose 130 patients who had undergone 8 weeks of risperidone monotherapy to examine the relationship between their response to risperidone and CYP2E1 polymorphisms. Clinical efficacy was assessed using the Brief Psychiatric Rating Scale (BPRS). Results: Statistically significant differences in allele or genotype frequencies were found between cases and controls at rs8192766 (genotype p = 0.0048, permutation p = 0.0483) and rs2070673 (allele: p = 0.0018, permutation p = 0.0199, OR = 1.4528 95%CI = 1.1487-1.8374; genotype: p = 0.0020, permutation p = 0.0225). In addition, a GTCAC haplotype containing 5 SNPs (rs3813867, rs2031920, rs2031921, rs3813870 and rs2031922) was observed to be significantly associated with schizophrenia (p = 7.47E-12, permutation p<0.0001). However, no association was found between CYP2E1 polymorphisms/haplotypes and risperidone response. Conclusions: Our results suggest that CYP2E1 may be a potential risk gene for schizophrenia in the Chinese Han population. However, polymorphisms of the CYP2E1 gene may not contribute significantly to individual differences in the therapeutic efficacy of risperidone. Further studies in larger groups are warranted to confirm our results. © 2012 Huo et al.

Huo R.,Shanghai JiaoTong University | Huo R.,Shanghai Genomepilot Institutes | Wei Z.,Shanghai JiaoTong University | Wei Z.,Shanghai Genomepilot Institutes | And 22 more authors.
Neuroscience Letters | Year: 2015

Evidence suggests that dopamine receptor D1 (DRD1) may be involved in the pathophysiology of schizophrenia and the pharmacodynamics of antipsychotics. We conducted a comprehensive pharmacogenomics study to investigate the association of genetic polymorphisms in DRD1 with treatment response to risperidone. Two independent cohorts of Han Chinese schizophrenic patients (. n=. 185) from two different geographic areas treated with risperidone monotherapy for 4 weeks and four SNPs (rs5326, rs4867798, rs4532 and rs686) in the DRD1 gene were analyzed. Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). The definition of risperidone response is based on a cut-off of 50% in terms of corrected percent change of PANSS score. The significant confounding effects of non-genetic factors were included as covariates for adjustment. No significant association of DRD1 polymorphisms with risperidone treatment response was found in either single marker or haplotype analysis in this study. The current results provide the first evidence that DRD1 polymorphisms may not influence the clinical efficacy of risperidone in Chinese schizophrenia patients. © 2014 Published by Elsevier Ireland Ltd.

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