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Background: Previous studies with biological and genetic evidence indicate that the myo-inositol monophosphatase 2 (IMPA2) gene may influence schizophrenia.This study sought to investigate whether genetic variations in IMPA2 are associated with susceptibility to schizophrenia in Han Chinese and whether the association is sex-specific.Methods: Seven single nucleotide polymorphisms (SNPs) were identified by sequencing the IMPA2 promoter region in 50 patients with schizophrenia.Five of these (rs971363,rs971362,rs2075824,rs111410794,and rsll1610121),as well as one (rs45442994,in intron 1) that was positively associated in another study,were selected for genotyping in 1,397 patients with schizophrenia and 1,285 mentally healthy controls.Genotype and allele frequencies were assessed by gender stratification.Results: 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)].Furthermore,we found a sex-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)].Conclusion: Our data suggests that IMPA2 rs2075824 strongly associated with schizophrenia in Han Chinese individuals.