Correlation Analysis Among Polymorphism Of Tryptophan Hydroxylase Isoform (TPH2) Gene (rs1386494) In MDD

ObjectiveMajor depressive disorder (MDD) is one of the most common psychiatric diseases. It is very significant that identify the pathogenesis of MDD. Several lines of evidence indicate that disturbances of the central serotonergic system are involved in the pathophysiology of affective disorders. Tryptophan hydroxylase (TPH), being the rate-limiting enzyme in the synthesis of the neurotransmitter serotonin (5-HT), plays a major role as candidate gene in several psychiatric disorders.TPH has two hypotypes:TPH1 and TPH2. It is demonstrate that in humans TPH1 and TPH2 are expressed in nearly equal amounts in several brain regions (frontal cortex, thalamus, hippocampus, hypothalamus and amygdala), with a predominant expression of TPH2 in the brain stem, the major locus of the serotonin-producing neurons, whereas TPH1 mRNA is exclusively present in peripheral tissues.It is maybeassociate between the polymorphisms in the TPH2 gene and major depressive disorder.Depending on differents genomics methods, Patients with MDD diagnosed according to the DSM-FV will be choose to makesure the associate between one singlenucleotide polymorphism (SNP) in the TPH2 gene and MDD in Han sample,which also include the associate between it and Therapeutic Effect of Fluoxetine.MethodsA total of 170 unrelated Han out-patients with MDD in the Psychiatric Department of the China Medical University diagnosed according to the DSM-IVand excluded the bipolar depression,drug addiction,alchohol rely and other severity health diseases.were included in the study. All patients were interviewed by experienced psychiatrists using the Structured Clinical Interview for DSM-IV disorders .222 ethnically matched subjects from the general population in health olunteers served as control group. We performed singlenucleotide polymorphism (SNP) studies by PCR and restricted fragment length polymorphism.ResultsThe results of the single SNP association analysis are presented that statistically significant evidence for association with MDD was detected. The SNP rs 1386494 yielded the most significant result, due to an increase of the A-allele in the cases (x~2＝4.837, P<0.05).Showing that the A-allele maybe associated with MD. None of significant association was detected between SNP rs 1386494 and the therapeutic effect by fluoxetine (P>0.05)or Severity of pathogenetic condition (P>0.05)and sex(P>0.05) in Han sample.ConclusionThe findings suggest that the TPH2 gene polymorphism SNP rs 1386494 is associated with MDD and may be not associated with the therapeutic effect by fluoxetine or Severity of pathogenetic condition and sex in Han sample. Our findings provide evidence for an involvement of genetic variants of the TPH2 gene in the pathogenesis of MDD . These results may open up new research strategies for the analysis of the observed disturbances in the serotonergic system in patients.