Background: Microarray studies of schizophrenic brains revealed decreases in the expression of myelin and oligodendrocyte-related genes. Of these genes, sex-determining region Y-box 10 (SOX10) is a major transcription factor modulating the expression of proteins involved in neurogenesis and myelination. The SOX10 gene is located on chromosome 22q13.1, a region repeatedly reported to show positive signals in linkage studies on schizophrenia.
Objective: This study was conducted to clarify the exact role of SOX10 in the pathophysiology of schizophrenia.
Methods: We performed an association analysis of SOX10 in a Japanese population of 915 schizophrenic patients and 927 controls. Genotyping was carried out using polymerase chain reaction restriction fragment length polymorphism.
Main results: One single nucleotide polymorphism of the SOX10 gene (rs139887) was selected as a haplotype tag single nucleotide polymorphism using 96 controls. A significant association was observed in the genotype and allelic frequency of this single nucleotide polymorphism between schizophrenic patients and controls (P=0.025 and P=0.009, respectively). Especially, a significant association was found in male patients, but not female patients. We also performed a mutational search of the whole coding region, branch site, and promoter region of SOX10 in 96 schizophrenic patients, but no potential functional polymorphisms were detected.
Conclusion: This study suggests that the SOX10 gene is related to the development of schizophrenia in the Japanese population.
Departments of aPsychiatry
bMedical Technology, Nagoya University Graduate School of Medicine, Nagoya
cDepartment of Psychiatry, Fujita Health University School of Medicine, Toyoake
dDepartment of Psychiatry, Teikyo University School of Medicine, Chiba Medical Center, Chiba, Japan
Correspondence to Professor Toshiya Inada, MD, Department of Psychiatry, Teikyo University, School of Medicine, Chiba Medical Center, Anesaki 3426-3, Ichihara-shi, Chiba 299-0111, Japan
Tel: +81 436 62 1211(ext 2902); fax: +81 436 62 1511;
Received 25 September 2006 Revised 29 December 2006 Accepted 29 December 2006