Tryptophan Hydroxylase Gene-G1066A Polymorphism And The Research Of The Relationship With Schizophrenia

Introduction5 - hydroxytryptamine ( 5 -HT) is an important material in humans metabolism, and distributes extensively in our tissues. 5 - HT is involved in many kinds of central nervous activities as a central neurotransmitter. 5 — HT s effective concentration is influenced by its enzymes which attribute in the synthesis and metabolism of the serotonin. Not only the enzymes but also its receptors and vectors can effect the function of 5 - HT in central nervous system.Tryptophan hydroxylase (TPH) is the rate - limiting enzyme in the biosynthesis of serotonin in the raphe neurons of the brain. Whether the physiological activity and the expression of 5 - HT are normal can contribute to the biosynthesis , it can reinforce or damp the action stability of 5 - HT and its metabolite, e-ven more the function in the central nervous system.The human TPH gene has been located in the chromosome region 11 p15.3 -pl4. The gene spans 29kbp and contains 13 exons, it translates to the TPH which is constructed with 444 amino acids. TPH gene contains a chort of variants, these polymorphisms distribute promoter upstream, intonlB, 1C,7,8and 9, in addition to a microsatellite repeat at 3' downstream.We select TPH gene - G1066 A site located in promoter upstream in our research, and investigate the genetic polymorphism in Northern Chinese Han. Further more approach the association between - G1066A and schizophrenia.Material and MethodsOrdering the primer by articles, we use PCR method to amplify the TPHgene - G1066A locus, and use Cfrl31 restriction endonucleases digest them, by PAGE followed sliver stain. We genotype the genes of 140 Chinese han and 133 Schizophrenia individuals.ResultsIn 140 Chinese han individuals, we found two alleles and three genotypes: homozygote GG was 93 individuals, its frequency was 0. 664;heterozygote GA was 42 individuals, its frequency was 0. 300;homozygote A A was 5 individuals, its frequency was 0. 036. Allele G frequency was 0. 814, allele A frequency was 0. 186. We found two alleles and three genotypes.In 133 Schizophrenia individuals, we found homozygote GG was 77 individuals, its frequency was 0. 579;heterozygote GA was 41 individuals, its frequency was 0. 308;homozygote A A was 15 individuals, its frequency was 0. 113. Allele G frequency was 0. 733 , allele A frequency was 0. 267.DiscussionThis study investigated the TPH gene - G1066A polymorphism in the Chinese Han and Schizophrenia frequency, by statistics analysis, the data obey the Hardy - Weinberg regulation. According to the - G1066A genotype and allele frequency in Chinese Han data, we conclude that the DP value is 0.486, the H value is 0. 300, the EPP value is 0. 129. This loci is middling discrimination power genetic system.To compare the Chinese Han individual with the Schizophrenia individual, the allele frequency distribution has a obviously statistic difference, p <0.05, and it demonstrates that A allele is the predisposing genes in schizophrenia.ConclusionOur study report the genotype frequency and allele frequency distribution of TPH gene - G1066A locus in Chinese han and Schizophrenia individuals, andprovide the necessarily data in forensic medicine. The Chinese han individual have highly discrimination power and EPP. The frequency has obviously difference between the two population (p < 0. 05) , and allele A has a high frequency in schizophrenia , we suppose that A allele is the predisposing gene in schizophrenia.