Identification of the N-acylsphingosine amidohydrolase 1 gene (ASAH1) for susceptibility to schizophrenia in a Han Chinese population.

Objectives: To study the involvement of the N-acylsphingosine amidohydrolase 1 gene (ASAH1) in the susceptibility to schizophrenia in the Han Chinese population.

Methods: We performed cDNA microarray analysis to exam the gene expression profile in six schizophrenic patients and six healthy controls. We evaluated the ASAH1 expression levels in 30 subjects with chronic schizophrenia and 30 healthy controls by using real-time polymerase chain reaction (PCR). A total of 254 unrelated probands with schizophrenia and their biological parents were also genotyped at three single nucleotide polymorphisms (SNPs: rs3753118, rs3753116, and rs7830490) of the ASAH1 gene for association analysis.

Results: In the microarray analysis, the ASAH1 gene was down-regulated in all schizophrenic patients compared with healthy controls. In real-time PCR, the ASAH1 expression levels for schizophrenic patients with positive family history were significantly decreased (P = 0.020). In the association analyses, two SNPs (rs7830490 and rs3753118) and one haplotype (rs7830490 (A)-rs3753116 (G)) of ASAH1 showed significant evidence of nominal associations with schizophrenia (P = 0.026; P = 0.046; P = 0.007, respectively). The haplotype remained statistically significant (empirical P = 0.045) after correction for multiple testing.

Conclusions: This study supports that the ASAH1 gene may be a potential candidate gene for schizophrenia in Han Chinese subjects.