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Association Between Tryptophan Hydroxylase Gene Polymorphism(T3792A) And Depression And Its Forensic Significance

Posted on:2009-03-23Degree:MasterType:Thesis
Country:ChinaCandidate:B WangFull Text:PDF
GTID:2144360242991366Subject:Forensic medicine
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Induction5-serotonin(5-hydroxytryptamine,5-HT)is a key material in the process of human metabolism,it is widely distributed in the body.As a central neurotransmitter,it is involved in a variety of neural activity.5-HT concentration in the blood,and its metabolism,as well as in the metabolic process involving enzymes,receptors,the carrier and other factors will affect 5-HT in the central nervous system of normal expression.Tryptophan hydroxylase(TPH)is a rate-limiting enzyme in the synthesis of 5-HT,which is mainly distributed in the brain and intestinal pheochromocytoma.The physical activity and the level of TPH,will affect the 5-HT concentration in the blood, will strengthen or weaken 5-TH and its strength in the role of metabolism,thereby affecting it in the central nervous system.The synthesis and metabolic pathways of 5-HT is as follows:Tryptophan→5-HT acid→5-HT→5-HT aldehyde→5-hydroxyl indole acetic acid(AAAD).The human tryptophan hydroxylase(TPH)gene has localized on the short arm of chromosome 11(11p15.3-p14),between markers D11S151 and D11S134.The gene spans a region of 29 kbp,and is composed of 13 exons,including exon 1(1A,1B,1C), 2-11,a total of 444 amino acids composition of this enzyme.TPH gene has a number of mutation points and genetic polymorphism,which polymorphic loci are located in the upstream promoter region,intron 1B,C1,intron 7, intron 8 and intron 9,but also in the downstream of the 3 region has a microsatellite repeat sequences.We investigate the Han group in northern China,Tibetan group and the group of patients with depression in the genetic polymorphism,and to explore TPH gene T3792A genetic polymorphism loci with depression and the relevance of the forensic significance.Materials and MethodsThe primers were designed according to sequence.We use ASPCR method to amplify TPH gene T3792A,and polyacrylamide gel electrophoresis in combination with silver staining method.we genotype 302 cases of the North Han Chinese individuals,135 cases of Chinese Tibetan individuals,113 cases of depression.Result302 Chinese Han cases of blood samples is detected by conventional electrophoresis genotype,and the detection is 78 cases of AA,169 cases of AT,55 cases of TT.The A allele frequency was 0.538,T allele frequency was 0.462.113 cases of depression patients blood samples is tested,and the detection is 44 cases of AA,52 cases of AT,17 cases of TT.The A allele frequency was 0.619,T allele frequency was 0.381.135 cases of Chinese Tibetan blood samples is tested,and the detection is 22 cases of AA,69 cases of AT,44 cases of TT.The A allele frequency was 0.419,T allele frequency was 0.581.DiscussionBased on 302 cases of Chinese Han individuals,135 cases of Chinese Tibetan individuals of TPH gene T3792A loci genetic polymorphism analysis,the genotype distribution compliance with the Hardy-Weinberg equilibrium.According to the allele frequencies and genotype frequencies of the TPH gene loci T3792A in Han population in northern China,and the China Tibetan group,we calculated,TPH gene loci T3792A in the Han population in northern China,the DP value is 0.587,the H value is 0.497, the EPP values is 0.187.Tibetan group in China,the DP value is 0.606,the H value is 0.487,the EPP value is 0.184.We conclude that the site in the two groups is a high capacity to identify the genetic marker system for forensic applications.This experimental study showed that,the distribution of TPH gene T3792A loci genotype frequencies between depression patients and healthy control group,there was a significant difference(x~2=4.422,P=0.035),with statistical significance.And in the patients with depression,the A allele frequency was significantly higher than that of the healthy controls.And the AA genotype frequency of depression patients is higher than that of the healthy control group.Therefore we speculate there is a linkage between TPH gene T3792A loci with A alleles and depression.It may be a susceptibility gene to depression.We compared the data we have obtained with the French Caucasian population allele frequency(A=0.660,T=0.340)reported in the literature.Han and Tibetan,Han and Tibetan,Tibetan and France Caucasian showed significant differences,suggesting that TPH gene T3792A loci genetic polymorphism may have racial,ethnic or geographical differences,it is an important genetic marker in human genetics research.Conclusion1.TPH gene T3792A loci in the Han population in northern China,the Tibetan population has a better polymorphism distribution,it can be an important application of genetic markers in forensic identification and paternity testing.2.In the Chinese Han population,the TPH gene T3792A loci mutation may be associated with depression.3.TPH gene T3792A genetic polymorphism loci has a racial difference.
Keywords/Search Tags:Tryptophan hydroxylase (Tryptophan Hydroxylase, TPH), Single nucleotide polymorphism (SNP), ASPCR, Han, Tibetan, Depression
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