Analysis Of GABA_A Receptor Gene With Schizophrenia In Northern Chinese Population

Objective: Schizophrenia (SCZ) is one of common, complex and serious psychiatric disorders affecting approximately 1% of the world's population. Its complexities can be characterized as follows: (1) the diagnosis of the disease relies on its clinical phenotype,however, incertitude of phenotype and difference in clinical presentation leads to ambiguity in diagnosis; (2) this disease is caused by multiple minor-effective genes, which increase the difficulty in related genetic researches; (3) typical phenotypic and genetic heterogeneity exists in this disease; (4) irregular dominance and incomplete dominance can be presented in schizophrenia. These complexities severely hinder the researches in pathogenesis of the disease.In the prevailing pathogenic model, SCZ is a disorder with abnormal synaptic connectivity in which major neurotransmission system are involved. One candidate system is the gamma aminobutyric acid (GABA) system, and various lines of evidence support its involvement in the SCZ. The present research was based on the previous work of our team which systematically screened the GABAA receptor and transporter 20 related genes of 86 single nucleotide polymorohisms (SNPs) in 80 paranoid schizophrenia and 108 controls and results and found that GABRG1 gene and the combind effect of GABRE/GABRQ/sex may be invoved in the patogenesis of paronid schizophrenia. Thus, the aims of the present study are: (1) to replicate the result acquired by previous work in larger sample in order to augment the analutical power.; (2) to explore the susceptible genes of a certain phenotype by stratifying patients using phenotype to increase the homogeneity.Methods: We collected patients which meet the diagnostic criteria of paranoid schizophrenia in DSM-IV, and finally 509 patients were recuited and in 410 patients, we collected the phenotype data by using positive and negative scale (PANSS). At the same time, 583 unrelated healthy controls were collected which matched sex and ethical. SNPs were genotyped by polymerase chain reaction (PCR) and PCR pruducts indirect sequencing. We used unphased software to analysis case-control test and quantitative traits test. Gene-gene interaction was test to use MDR software.Results: (1) Our results indicated that GABRG1, GABRE and GABRQ gene may not play a major role in the pathogenesis of paranoid schizophrenia. (2) The genotype of SNP rs381051 in GABRQ gene has a strong association with hallucination behaviors (P=0.0068, 1000 permutation test P=0.02498).(3) The rs976156-rs1497568 haplotype in GABRG1 gene may be has a relationship with the phenotype--lack of spontaneity and flow of conversation and has a trend association with grandiosity.(4) There may be an association between rs2256882 (GABRE)-rs3810651 (GABRQ) haplotype and conceptural disorganization in positive symptom scale, emotional withdrawal, poor rapport and passive/apathetic social withdrawl in negative symptom scale.Conclusions: We considered that the GABRG1, GABRE and GABRQ gene encoding GABRA receptor subunits may not play a key role in pathogenesis of paranoid schizophrenia but may have a relationship with phenotype susceptivity.