The Genetic Polymorphism Of-T457C Locus In TPH Gene: Its Association With Depression And Practical Value In Forensic Medicine

Introduction5-hydroxytryptamine(5-HT)exists extensively in human tissues.As one of central neurotransmitters,5-HT plays a key role in many CNS activities,including emotional control,sleep regulation,anxiety,alcohol abuse,sexual behaviour and so on. A lot of mental disorders are concerned with 5-HT.Many factors attribute in the synthesis and metabolism of 5-HT and influence its function in central nervous system. Whether the expression of tryptophan hydroxylase is normal can play an importmant role in metabolic procedure of 5-HT.Tryptophan hydroxylase(TPH)is the rate-limiting enzyme in the biosynthesis of serotonin,which catalyze tryptophan into 5-hydroxytrptophan.Whether the expression of TPH is normal can determine the quality and quantity of 5-HT,which would subsequently influence some regulation procedure in central nervous system.Human TPH gene has been located in the chromosome region 11p15.3-p14.The gene spaning 29kbp and containing 13 exons,translates to the TPH which is constructed with 444 amino acids.TPH gene contains a chort of polymorphic variants, these polymorphisms scatter in promoter region,inton1B,1C,7,8 and 9.In the present study,-T457C locus located in inton 8 of TPH gene was selected, and investigated in Chinese Han and Tibetan nationalities.In addition,a group of patients with depression were selected,and the association between-T457C and depression was investigated. Material and MethodsOrdering the primer by articles,-T457C locus of TPH gene was amplified using PCR technology.Then,the PCR products were digested with NlaⅢrestriction endonucleases.After polyacrylamide gel electrophoresis followed with standard silver stain,clear allelic discrimination was achieved.284 Chinese han,142 Tibetan and 111 depression individuals were investigated.PCR products of several samples were sequenced to validate the results of the above RFLP procedure.ResultsIn 284 Chinese ban individuals,60 were TT homozygote(0.211),148 CT heterozygote(0.521),and 76 CC homozygote(0.268).The frequency of T-allele was 0.472,and C-allele 0.528.In 142 Tibetan individuals,30 were TT homozygote(0.211), 64 CT heterozygote(0.451),and 48 CC homozygote(0.338).The frequency of T-allele was 0.437,and C-allele 0.563.In 111 depression individuals,31 were TT homozygote (0.279),51 CT heterozygote(0.460),and 29 CC homozygote(0.261).The frequency of T-allele was 0.509,and C-allele 0.491.DiscussionThis study investigated the -T457C locus of TPH gene in Chinese Han,Tibetan and depression groups.The distribution of its genetic data complied with the law of Hardy-Weinberg equilibrium.In Chinese Han group,the values of DP,H,and EPP were 0.612,0.521,and 0.187,respectively.In Tibetan group,the values of DP,H,and EPP were 0.638,0.451,and 0.185,respectively.This locus possessed high discrimination power.The distributions of alleles and genotypes did not exhibit significant difference between healthy Han individuals and patients(p＞0.05).However,the frequencies of T-allele and TT homozygotes were much high in depression group.In addition,the frequency distribution of TT homozygote were significantly different between health female group and female patients(p=0.029).These results indicated that the T-allele might be related to depression.The frequency distributions of alleles and genotypes did not exhibit significant difference between Chinese Han and Tibetan groups(p＞0.05).However,both of them were significantly different with French population(p=0.001,p=0.050,respectively). These results showed that the -T457C locus might be different between races.ConclusionThe -T457C locus of TPH gene exhibited high genetic polymorphism in Chinese Han and Tibetan nationalities so that it might be valuable in forensic individual identification and paternity test.This locus could be used as an important marker in human genetics research.In addition,our results suggested that this locus might be related to depression.