title: Genetic polymorphisms in CYP2E1: association with schizophrenia susceptibility and risperidone response in the Chinese Han population.
abstract: 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.
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Ran
authors.initials: R
authors.lastname: Huo
authors.forename: Kefu
authors.initials: K
authors.lastname: Tang
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Wei
authors.forename: Lu
authors.initials: L
authors.lastname: Shen
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Xiong
authors.forename: Xi
authors.initials: X
authors.lastname: Wu
authors.forename: Jiamin
authors.initials: J
authors.lastname: Niu
authors.forename: Xia
authors.initials: X
authors.lastname: Han
authors.forename: Zhengan
authors.initials: Z
authors.lastname: Tian
authors.forename: Lun
authors.initials: L
authors.lastname: Yang
authors.forename: Guoyin
authors.initials: G
authors.lastname: Feng
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Shengying
authors.initials: S
authors.lastname: Qin
mesh_terms: D024506:5' Flanking Region; D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018967:Risperidone / Q000494:pharmacology; D012559:Schizophrenia / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D019392:Cytochrome P-450 CYP2E1; D018967:Risperidone