The Polymorphisms Of -855G/C And -1140G/A In GRIN1 Gene And The Genetic Correlation To Schizophrenia And Depression

Human nervous system is the most complex system in nature, and neuron is structural unit of nerve tissue. The interaction among neurons is associated with the neurotransmitter. Schizophrenia (SP) is defined as a group of clinical manifestation with unknown etiology, loose thinking, illogical association, absurd paranoia, inappropriate or insipid passion, and social impairment. SP is an important aspect of forensic expertise. Besides environmental factors, as a quality defect, genetic factors have been clearly confirmed in SP incidence.Glutamate acid (Glu) is the essential excitatory amino acid of the body, which is the most abundant excitatory neurotransmitter of the central nervous system in mammals and involved in a variety of regulation of important functions in nervous systems. Glu was stored in vesicles of the nerve endings. As synaptic transmission, Glu releases in the form of exocytosis, and activates postsynaptic glutamate receptors. After activation, Glu make the effector produce a marked effect thus changing the cell's membrane potential and biochemical status. Glu plays an important role in learning, memory, nerve conduction and so on.In general, the promoter regions of gene are important targets in transcription regulation and translation, whose variation in gene's internal sequence may affect the product of protein expression. As is known, single nucleotide polymorphism (SNP) loci of the promoter region of GRIN1 gene has only provided a very small data in Chinese population. In view ot the existing international and domestic research of GRIN1 gene SNP loci associated with SP, -855G/C and -1140G/A, two SNP loci located in GRIN1 gene promoter region were selected in this study, so that the genetic polymorphisms in the Han population in northern China were investigated to explore its relationship with SP and depression, and to provide reference data for forensic personal identification, parentage testing and the study of the human spirit status.Materials and MethodsGenomic DNA extraction was performed, then according to the target sequence to design primers, PCR restriction fragment length polymorphism (PCR-RFLP) method, polyacrylamide gel electrophoresis (PAGE) and silver staining were applied in -855G/C and -1140G/A to genotype genetic polymorphisms in 183 controls of Northern Chinese Han individuals, 172 cases of schizophrenic patients and 115 cases of simple depression patients. They were analysized to calculate the relevant forensic data and discussed with case-control study.Results1. There is no deviation from Hardy-Weinberg equilibrium law in 183 controls of Northern Chinese Han individuals, 172 cases of schizophrenic patients and 115 cases of simple depression patients.2. The data of genotype distribution and allelic frequencies of -855G/C of GRIN1 gene is listed in Table 1.Table 1. Genotype and allelic frequencies of -855G/C of GRIN1 gene in controls, schizophrenic patients and depression patients 3. The data of genotype distribution and allelic frequencies of -1140G/A of GRIN1 gene is listed in Table 2.Table 2. Genotype and allelic frequencies of -1140G/A of GRIN1 gene in controls, schizophrenic patients and depression patients4. The forensic parameters such as probability of discrimination power (DP), heterozygosity (HE), probability of exclusion (PE) and polymorphism information content (PIC) of -855G/C and -1140G/A of GRIN1 gene are listed in Table 3.Table 3. The forensic parameters of -855G/C and -1140G/A of GRIN1 gene in the Han population in northern China5. For -1140G/A locus of GR1N1 gene, there is significant statistical difference between controls and SP, as well as between women controls and women SP accordingto theχ~2 test.Conclusion1. There is much more deviation from the distribution of genotype and allelic frequency of -1140G/A than that of -855G/C of GRIN1 gene, and the latter is superior to the former in forensic personal identification and parentage testing.2. The polymorphisms of -1140G/A of GRIN1 gene may be associated with SP. and women is at high risk. The allele A is the susceptive allele. 3. In GRIN1 gene, the allele A of -1140G/A is at the close genetic linkage with the allele G of -855G/C locus.4. There is ethnic or regional difference in the genetic polymorphism of -855G/C and -1140G/A loci of GRIN1 gene.