Tryptophan Hydroxylase Gene A218C Sites Of Genetic Polymorphism And Depression-related Research And Forensic Significance

IntroductionSeveral lines of evidence indicate that abnormalities in functioning of the central serotonergic system have been implicated in the pathogenesis of depressive illness and suicidal behavior. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of serotonin, therefore, it may play an important role in regulation or control of serotonin functions. Recently, polymorphisms of the TPH gene have been identified as being associated with depressive illness, such, it is one of the major candidate genes for psychiatric and behavioral disorders associated with pathogenesis events involving dysfunction of the 5-HT system.This gene is located on short arm of chromosome 11 (11p15.3-p14), spans a region of 29 kb which contains at least 11 exons. Nielson et al identified two informative TPH single nucleotide polymorphisms (SNPs), A218C (rs1800532) and A779C (rs1799913), both located in intron7. There are many reports of A218C, but the result is inconsistent.The aim of the present investigation was to determine whether there is an association between TPH gene polymorphism and major depression as well as to investigate the genetic polymorphism in Northern Chinese Han and Zang.Material and methodsOrdering the primer by articles, we use PCR method to amplify the TPH gene A218C locus, and use BfaI restriction endonucleases digest them, by PAGE followed sliver stain. We genotype the genes of 292 Chinese Han (169males, 123 females), 107 depressed individuals (42males,65females) and111 Chinese Zang (45males,66females). ResultsIn 292 Chinese Han individuals, we found two alleles and three genotypes: homozygote AA was 66 individuals, its frequency was 0.226; heterozygote AC was 145 individuals, its frequency was 0.497; homozygote CC was 81 individuals, its frequency was 0.277. Allele A frequency was 0.474, allele C frequency was 0.526.In 107 depressed individuals, we found homozygote AA was 32 individuals, its frequency was 0.299; heterozygote AC was 51 individuals, its frequency was 0.477; homozygote CC was 24 individuals, its frequency was 0.224. Allele A frequency was 0.537, allele C frequency was 0.463.In 111 Chinese Zang individuals: homozygote AA was 23 individuals, its frequency was 0.207; heterozygote AC was 52 individuals, its frequency was 0.469; homozygote CC was 36 individuals, its frequency was 0.324. Allele A frequency was 0.441, allele C frequency was 0.559.DiscussionThis study investigated the TPH gene A218C polymorphism in the Chinese Han, depressed and Chinese Zang frequency by statistics analysis, the data obey the Hardy-Weinberg equilibrium. According to the A218C genotype and allele frequency in Chinese Han data, we conclude that the DP value is 0.625, the EPP value is 0.187. In Chinese Zang, the DP value is 0.632, the EPP value is 0.186. This loci is middling discrimination power genetic system.To compare the Chinese Han individual with the Depressed individual, the allele frequency distribution has not a obviously statistic difference, p>0.05.and the sex has not a obviously statistic difference either, p>0.05.To compare the Chinese Han and Zang individual with other countries individual, the allele frequency distribution has changed with nation and region.ConclusionOur study report the genotype frequency and allele frequency distribution of TPH gene A218C locus in Chinese Han and Chinese Zang, and provide the necessarily data in forensic medicine. Both the Chinese Han and Zang individual have highly DP and EPP. The frequency has not obviously difference between the Chinese Han population and depressed individuals (p>0.05) . and the sex has not a obviously statistic difference either, p>0.05. and the allele frequency distribution has changed with nation and region.