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Identify The Htr2 A Gene Region In Patients With Depression

2285 words - 9 pages

The HTR2A gene encodes the 5-hydroxytryptamine (serotonin) receptor at the 2A region. The HTR2A gene is located on chromosome 13, containing 3 exons and 2 introns spanning 20 kb (Myers et al, 2007). Genetic variation in the HTR2A regulatory region is due to the action of several single nucleotide polymorphisms (SNPs) on the regulatory region (Myers et al, 2007). These SNPs include the -1438A/G, -783A/G and -1420C/T SNPs, the - 1420C/T and -1438A/G SNPs (Myers et al, 2007). The most widely studied SNP on the HTR2A gene region is the -1438A/G-allele polymorphism, which occurs at the highest allele frequency of 55% upstream the core of the promoter (Myers et al, 2007). The -1438A/G SNPs as well as the T102C SNP (both found to be in complete linkage disequilibrium with each other) have been associated with many psychiatric disorders including obsessive–compulsive disorder, major depressive disorder, schizophrenia and various eating disorders (Myers et al, 2007). The results of extensive research on the associations of those SNPs with the various psychiatric disorders have however been inconsistent (Kishi et al, 2009).

The serotonin receptors (5-HT) for which the HTR2A gene encode are involved in excitatory and inhibitory transmission of many neurotransmitters (e.g. Glutamate, dopamine, norepinephrine etc) as well as hormonal secretions (e.g. oxytocin, vasopressin, substance P etc) (Tecott et al, 1994). Serotonin receptors are a group of G-Protein coupled receptors (GPCRs) (receives molecules from outside and uses them to activate signal transduction inside the cell) and ligand-gated ion channels (LGICs) located in the central nervous system and the pheripheral nervous system (Tecott et al, 1994). The 5-HT receptors are activated by the neurotransmitter serotonin.

Serotonin is synthesized in the neurons from the essential amino acid L-tryptophan (TRP) (Brown, Van Praag 1991). Serotonin affects many somatic processes, these include sleep, sexual activity, mood, circadian rhythms, motor activity, neuroendocrine function, cognitive function and anxiety (Meltzer, Lowy 1987). It is therefore, on the basis of those functions that it was hypothesised that disturbances in serotogernic mechanisms in relation to abnormalities in other monoamine neurotransmitters (e.g. dopamine, epinephrine) may contribute to symptoms seen in various psychiatric disorders (Brown, Van Praag 1991).
Various clinical and pharmaceutical studies have investigated a possible link between the HTR2A gene and the psychiatric disorder depression (Choi et al, 2004). Several post-mortem studies have revealed that there is an increased level of HTR2A gene in the frontal cortex of depressed or suicide victims (Arango et al, 1990). More specifically increasing evidence has shown the association of the -1438A/G SNP in the HTR2A promoter region in patients with major depressive disorder (MDD) (Choi et al, 2004).

Major depressive disorder is a complex, multifactorial trait...

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