A polymorphism of the ABCA1 gene confers susceptibility to schizophrenia and related brain changes

Objective: The ATP-binding cassette transporter A1 (ABCA1) mediates cellular cholesterol efflux through the transfer of cholesterol from the inner to the outer layer of the cell membrane and regulates extracellular cholesterol levels in the central nervous system. Several lines of evidence have indicated lipid and myelin abnormalities in schizophrenia. Method: Initially, we examined the possible association of the polymorphisms of the ABCA1 gene (ABCA1) with susceptibility to schizophrenia in 506 patients with schizophrenia (DSM-IV) and 941 controls. The observed association was then subject to a replication analysis in an independent sample of 511 patients and 539 controls. We further examined the possible effect of the risk allele on gray matter volume assessed with magnetic resonance imaging (MRI) in 86 patients with schizophrenia (49 males) and 139 healthy controls (47 males). Results: In the initial association study, the 1587. K allele (rs2230808) was significantly more common in male patients with schizophrenia than in male controls. Although such a significant difference was not observed in the second sample alone, the increased frequency of the 1587. K allele in male patients remained to be significant in the combined male sample of 556 patients and 594 controls. Male schizophrenia patients carrying the 1587. K allele had a smaller amount of gray matter volume than those who did not carry the allele. Conclusion: Our data suggest a male-specific association of the 1587. K allele of ABCA1 with susceptibility to schizophrenia and smaller gray matter volume in schizophrenia.