Tryptophan Hydroxylase Gene(TPH1)-1067G/A,-347T/G Polymorphism Associated With Schizophrenia And Its Forensic Significance

IntroductionThe human nervous system in nature is the most complex system, neurons of the nervous structure of the organization unit, the interaction between neurons is the neurotransmitter interrelated. Schizophrenia (schizophrenia, SP) for a group of unknown diseases, clinical manifestations were thought process loose, illogical associations, absurd delusion, emotional inappropriate or flat, and social functional impairment as the main symptoms. SP is an important part of forensic expertise. In addition to certain environmental factors outside, SP incidence of quality defects Genetic factors have also been clearly confirmed.Tryptophan hydroxylase (tryptophan hydroxylase, TPH) is a 5-HT synthesis rate-limiting enzyme, catalytic tryptophan generates 5-hydroxy tryptophan. From 444 amino acids, which are mainly distributed in the brain and enterochromaffin cells. High specificity of this enzyme, the content less low activity, TPH levels of physical activity and expression of the normal or otherwise affect the amount of 5-HT synthesis, enhance or diminish 5-HT and its metabolites in the role of strength, thereby affecting its the central nervous system function [6] has been found that two kinds of TPH: namely TPH1 and TPH2 [7]. TPH1 by 444 amino acids. Only in the few specific tissues, they are mast cells, monocytes, Langerhans (s) cells on the island ofβcells, the digestive tract, and pancreatic cells, in the central nervous system (CNS), brain Dry spinal cord neurons and pineal cells are also distributed. Research and analysis of this enzyme can be on people's estimates of certain mental state is conducive to what found by people in the state of mind and can thus be viewed as a candidate gene for mental disorder symptoms [8]. This study investigated TPH1 gene-1067G/A,-347T/G locus and schizophrenia in northern Chinese Han population genetic polymorphism of its forensic application and the reference value for the diagnosis of schizophrenia.Materials and Methods212 cases (male 95 cases, female 117) in northern Chinese Han healthy unrelated individuals elbow vein blood samples provided by the China University of Medical, within three generations by the survey was no family history of mental illness; 191 cases (male 92 cases, female 99 cases) in patients with SP Han blood samples provided by the China University of Medical, taken from Kaiyuan, Liaoning institutions, and by disease subtype classification of 95 cases of paranoid schizophrenic patients,88 patients with schizophrenia are not stereotyping. The diagnosis of SP patients fulfilled the American Psychiatric Association "Diagnostic and Statistical Manual of Mental Disorders," 4th edition (DSM-IV) and "Chinese Classification and Diagnostic Criteria of Mental Disorders," 3rd edition (CCMD3).By genomic DNA extraction, depending on the target sequence to design primers, applied PCR restriction fragment length polymorphism (PCR restriction fragment length polymorphism, PCR-RFLP) method combined with polyacrylamide gel electrophoresis detection of TPH1 gene-1067G/A,—347T/G genetic polymorphism of DNA fragments separated by PAGE and silver staining methods spectral type, calculate the relevant forensic data and case-control study.Results1,212 cases in northern Chinese Han individuals,191 cases of SP by the degree of matching of the individual genotype test, are consistent with Hardy-Weinberg equilibrium.2,In the 212 cases in northern Chinese Han individuals, TPH1 promoter-1067G/ A,-347T/G locus closely linked, were found in three kinds of genotypes and haplotypes of two kinds:AA-GG homozygotes was 143 cases, its frequency was 0.6745; hybrid AG-GT was 63 cases, its frequency was 0.2972; homozygote GG-TT was 6 cases, its frequency was 0.0283. AG haplotype frequency was 0.8231, GT haplotype frequency was 0.1768.3,In the 191 cases of SP patients, AA-GG 171 cases, a frequency of 0.9000; AG-GT for 18 cases, a frequency of 0.0947; GG-TT for 1 case, a frequency of 0.0053.4,SP comparison between patients and controls, haplotype frequency distribution of differences between groups P<0.05. The various groups, by gender group, SP groups according to clinical subtypes can be seen in comparing:SP in patients with men and the control group compared haplotype frequencies, P<0.05. SP patients and control group women, haplotype frequency comparison, P<0.05. Paranoid SP patients and control group haplotype frequencies compared to P<0.05. Undifferentiated SP patients and control group compared haplotype frequencies, P<0.05.5,TPH1 gene-1067G/A,-347T/G polymorphism loci in the Han nationality in northern China, its DP value is 0.4559, H value is 0.2972, PE value is 0.1244,PIC value of0.2489.Discussion1,This study investigated the TPH1 gene promoter region haplotype in the northern Chinese Han patients with SP frequency distribution, after statistical analysis showed that haplotype AG distribution in the SP patients was significantly higher. Haplotype AG may be a risk factor SP,-347T/G polymorphism sequence variation may be minor changes to the tissue-specific expression of TPH enzymes affecting 5-HT biosynthesis.2,According to TPH1 promoter-1067G/A,-347T/G polymorphism loci in the Han nationality in north China, haplotype frequencies and genotype frequencies were calculated:the haplotype locus DP value is 0.4559, H value is 0.2972, PE value is 0.1244, PIC value is 0.2489.The site belongs to a moderate ability to identify the genetic marker system for forensic identification and paternity testing has a certain application value. Conclusion1,TPH1 gene-1067G/A,-347T/G polymorphism may relate to SP related, and women's susceptibility to,-1067G/A in the A allele and-347T/G in the G allele may be disease susceptibility alleles. A-G haplotype may be associated with SP2,TPH1 promoter-1067G/A site in the A allele and-347T/G in the G allele is closely linked genetic;-1067G/A site in the G allele and-347T/G The T allele is closely linked genetically.3,TPH1 gene-1067G/A,-347T/G polymorphism loci of genetic polymorphism of the existence of national or regional differences.4,TPH1 promoter region-1067G/A and-347T/G loci in northern Chinese Han population has a good distribution of genetic polymorphisms in forensic individual identification and paternity testing can have a certain value.