Relationship Between The C825T Polymorphism Of Gβ 3 Gene And Clinical Response Of Fluoxetine

BackgroundMajor depression is one of common, severe and chronic psychiatric disorders with high rate of prevalence and relapse, suicide is also very common; it represents heavy burden of disease on society and bring about longtime complaints of patients a. To date, However, there was a non-full-satisfaction therapeutic effect of antidepressants and it always take more than six weeks to estimate whither to prescribe the same antidepressant continually or not. A prognosticating system of therapeutic effect of antidepressants is needed for major depression patients to realize individualized treatment.Pharmacogenomics was based on functional genomics and molecular pharmacology, elucidating the inherited nature of these differences in drug response mainly by means of analyzing the genetic variations of DNA and monitoring the gene expression pattern. It can not only improve disease diagnosis and predict the potential drug response but also speed up drug discovery and develop highly individualized treatment mode. The achievement of human genome project had provided numerous single nucleotide polymorphism, which facilitated the investigation of Pharmacogenetics and pharmacogenomics. An object of the Pharmacogenomics of major depression is to establish a prognosticating system of therapeutic effect of antidepressants, instructing rational administration,elevating security and efficacy of medicine, refraining from side effect. The pharmacogenoraics of depression will supply spacious perspective for the treatment of depression.Second messenger hypothesis of major depression consider hypofunction of cyclic adenosine monomphsopate as the key point of pathomechanism and elevating the function of cyclic adenosine monomphsopate was the syn-therapeutic-pathway-site of antidepressants. Heterotrimeric guanine nucleotide regulatory protein is ubiquitously expressed as mediators of stimuli from heptahelical receptors, but also receptors with intrinsic tyrosine kinase activity, into all cells of the human body. They are composed of α-, β-, γ-subunits, β γ dimers forming a functional monomer. In the non-activated state G protein α-subunits bind GDP, which upon interaction of the α-subunits with an activated receptor is released in exchange for GTP. GDP release and GTP binding initiate G protein activation. Subsequently, G protein α- and β γ-subunits dissociate and both α - and β γ -subunits can activate the adenylyl cyclase system, which ultimately results in elevating the function of cyclic adenosine monomphsopate. GNB3, the coding gene of G- protein beta 3 subunit, is located on chromosome 12pl3. All cell lines with increased G protein activation the nucleotide T at position 825 of the cDNA although the published cDNA sequence reported the nucleotide C at this respective position. All cell lines with low G protein reactivity were derived from homozygous C825 allele carriers. C825T exchange does not change the encoded amino acid (serine), however, with the 825T allele expressed a truncated splice variant of Gβ3, termed Gβ3s. Alternative splicing of the gene occurs through the use of a cryptic splice site located within exon 9, in which 41 amino acids are deleted. C825T is a functional single nucleotide polymorphism. The exchange has an impact of the structure and function of G protein and then also has an impact of the signal transmission in second messenger system. So GNB3C825T was one of the potential affectoi contributing to the therapeutic effect of antidepressant.ObjectiveIt is the purpose of the present study to investigate the relationship between the C825T polymorphism of Heterotrimeric guanine nucleotide regulatory protein beta3 subunit gene and the therapeutic effect of fluoxetine that is one of the selective serotonin re-uptake inhibitors. Our results may be helpful to establish a prognosticating system of therapeutic effect of antidepressants and an individualized treatment system, which is useful for instructing rational administration.Method1. Major depression patients were enrolled according to the fourth ed...