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

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 35; no. 8; pp. 1877 - 1883
• Main Authors: Ota, Miho, Fujii, Takashi, Nemoto, Kiyotaka, Tatsumi, Masahiko, Moriguchi, Yoshiya, Hashimoto, Ryota, Sato, Noriko, Iwata, Nakao, Kunugi, Hiroshi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.12.2011; Elsevier
• Subjects: Adult; Adult and adolescent clinical studies; ATP Binding Cassette Transporter 1 - genetics; ATP-binding cassette transporter A1; Biological and medical sciences; Brain - pathology; Case-Control Studies; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Magnetic Resonance Imaging; Male; Medical sciences; Middle Aged; Nerve Fibers, Unmyelinated - pathology; Neuropharmacology; Organ Size; Pharmacology. Drug treatments; Polymorphism; Polymorphism, Single Nucleotide; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Schizophrenia; Schizophrenia - genetics; Schizophrenia - pathology; Sex Factors; Voxel based morphometry; DSM-IV; GWAS; MRI; Schizophrenia; CNS; mRNA; ANCOVA; HDL; SPM; Voxel based morphometry; SNP; ANOVA; FDR; FWE; LDL; HWE; ABCA1; VBM; IL1β; TE; MINI; DNA; ATP-binding cassette transporter A1; PCR; TR; Polymorphism; Psychosis; Sensitivity; Gene; Central nervous system; Genetics; Morphometry; ABC transporter; Encephalon
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2011.07.012

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. 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). In the initial association study, the 1587K 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 1587K allele in male patients remained to be significant in the combined male sample of 556 patients and 594 controls. Male schizophrenia patients carrying the 1587K allele had a smaller amount of gray matter volume than those who did not carry the allele. Our data suggest a male-specific association of the 1587K allele of ABCA1 with susceptibility to schizophrenia and smaller gray matter volume in schizophrenia. ► The 1587K allele was more frequent in male schizophrenic patients than controls. ► There were no difference in the genotype distribution for rs2230808 in women. ► Gray matter volume was reduced in male schizophrenia patients with the 1587K allele.