title: A promoter polymorphism rs2075824 within IMPA2 gene affecting the transcription activity: possible relationship with schizophrenia.
abstract: Previous studies with biological and genetic evidence indicate that the myo-inositol monophosphatase 2 (IMPA2) gene may influence schizophrenia. We performed a genetic association study in Han Chinese cohorts. Five single nucleotide polymorphisms within IMPA2 promoter region (rs971363, rs971362, rs2075824, rs111410794 and rs111610121), as well as one (rs45442994, in intron 1) that was positively associated in another study, were selected for genotyping in 1397 patients with schizophrenia and 1285 mentally healthy controls. Genotype and allele frequencies were assessed by gender stratification. Interestingly, rs2075824 showed a strong association with schizophrenia (P = 4.1 × 10-4), and the T allele was more frequent in cases than controls [P = 5.6 × 10-5, OR (95% CI) = 1.26 (1.13-1.41)]. In vitro promoter assay showed that the transcription activity of the T allele promoter was higher than that of the C allele promoter and the T allele of rs2075824 contributed to risk for schizophrenia. By stratifying males and females, we found a gender-specific association for IMPA2 and schizophrenia: the T allele of rs2075824 was more frequent in male cases compared with male controls [P = 1.4 × 10-4, OR (95% CI) = 1.33 (1.15-1.55)]. Our data suggest that a promoter polymorphism of IMPA2 possibly contributed to risk for schizophrenia by elevating transcription activity in Han Chinese individuals.
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Shanghai General Hospital, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Shanghai General Hospital, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Shanghai General Hospital, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Hui-Rong
authors.initials: HR
authors.lastname: Dai
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Shanghai General Hospital, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Shanghai General Hospital, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Lin
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Shanghai General Hospital, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Shanghai General Hospital, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Shanghai General Hospital, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Shanghai General Hospital, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Wang
authors.affiliation: Department of Central Laboratory, Wuxi Mental Health Center, Wuxi, Jiangsu, China.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Yuan
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Shanghai General Hospital, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D012559:Schizophrenia / Q000201:enzymology* / Q000235:genetics*; D012727:Sex Characteristics; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase
keywords: Han Chinese; SNPs; myo-inositol monophosphatase 2; schizophrenia