Association Study Of GRIN2D Gene And Schizophrenia In Northern Chinese Han Population

Objective:Schizophrenia is one of the most common,complex and serious psychiatric disorders while its molecular etiology remains unknown.The glutamate hypothesis is becoming a hot spot in the field of schizophrenia research.Our work is to explore the association between GRIN2D gene and Schizophrenia,and to investigate the etiology of schizophrenia from the view of epigenetic,whether the level of methylation of GRIN2D is association with schizophrenia.Methods:In the present case-control study,a total of 455 patients with paranoid schizophrenia and 584 matched normal controls were recruited.The phenotype data were assessed by using Positive and Negative Syndrome Scale(PANSS).9 tag single nucleotide polymorphisms(tagSNPs) were selected in this study and genotyped by polymerase chain reaction(PCR) and direct sequencing of PCR products.The level of methylation of GRIN2D between patients with Schizophrenia and controls were detected by BSP.Finally,we use UNPHASED and Haploview softwares to analyze data of the association study,while use DNAMAN and QUMA softwares to compare the level of methylation.Results:(1) No significant differences were observed in allelic or genotypic frequencies of GRIN2D gene between the patients with Schizophrenia and controls.(2) A strong association was found between rs3786746(T)-rs892200(C) haplotype and paranoid schizophrenia(P=6.478e-6,10000 permutation test P=2.00e-3).(3)The allele C of rs276721 in GRIN2D gene has a strong association with hallucination behaviors (P=0.0023,10000 permutation test P0.0199.(4)The rs276721(C)- rsl654670(G) haplotype may has a relationship with hallucination behaviors(P=6.475e-4,10000 permutation test P=0.0229) and the rsl643490(A)-rs892200(C) haplotype may has a relationship with stereotyped thinking(P=0.0014,10000 permutation test P=0.043).(5) No significant differences were showed at the level of methylation of GR1N2D between the patients with Schizophrenia and controls.Conclution:GRIN2D gene may associate with schizophrenia and its partial phenotype susceptivity.And DNA methylation in its CpG-island may not play a key role in the etiology of schizophrenia.