Objective: Copy number variations encompassing the chromosome 15q11-q13 region have been implicated in the pathogenesis of several neurodevelopmental disorders including schizophrenia. The study aimed to investigate whether the GABRB3 gene mapped to 15q12 was associated with schizophrenia.
Materials and methods: We resequenced the promoter and all the exonic regions of the GABRB3 gene in 349 patients with schizophrenia and 386 control participants from Taiwan using the Sanger sequencing method. We also used a reporter gene assay to assess the functional impact of variants identified from the promoter region.
Results: We identified a total of six common single nucleotide polymorphisms and eight rare variants in this sample. No genetic association of these common single nucleotide polymorphisms with schizophrenia was detected. A missense mutation Y402H at exon 9 was detected in two patients and two controls. Polyphen-2 predicted that the impact of this variant was benign. In addition, we identified two patient-specific variants at the promoter of GABRB3 that showed significantly increased promoter activity in a reporter gene assay.
Conclusion: The identification of two private patient-only variants at the promoter region with enhanced promoter activity supports the rare allele hypothesis of schizophrenia and suggests that increased GABRB3 expression may confer an increased risk of schizophrenia.
aInstitute of Medical Sciences, Tzu-Chi University
bDepartment of Anesthesiology, Buddhist Tzu-Chi General Hospital
cDepartment of Psychiatry, Yuli Mental Health Research Center, Taipei Veterans General Hospital, Hualien
dDepartment of Psychiatry, Chang Gung Memorial Hospital at Linkou
eChang Gung University College of Medicine, Taoyuan, Taiwan
Correspondence to Chia-Hsiang Chen, MD, PhD, Department of Psychiatry, Chang Gung Memorial Hospital at Linkou, 5 Fusing Street, Gueishan, Taoyuan 33300, Taiwan Tel: +886 3 3281200 x2439; fax: +886 3 3280267; e-mail: firstname.lastname@example.org
Received July 6, 2013
Accepted April 10, 2014