We found that the association of the HTR2A-1438A/G polymorphism with SZ depends on the ethnic origin of the study population, and this genetic variant does not modify the susceptibility to BD or MDD.
The serotonin 2A (5-HT2A) receptor gene has been implicated in the pathogenesis of suicidal behavior by a genetic association between the 5-HT2AC102T silent polymorphism and suicidality in patients with major depression.
The purpose of this study was to determine the relationship between the -1438A/G polymorphism in the 5-HTR2A gene and the response to citalopram in a Korean population with major depressive disorder (MDD).
Pharmacological studies have yielded valuable insights into the role of the serotonin 2A (5-HT2A) receptor in major depressive disorder (MDD) and antidepressant drugs (ADs) response.
Accordingly, two single nucleotide polymorphisms of the HTR2A gene (rs6314 ie His452Tyr and rs6313 ie rs6313" genes_norm="3356">102C/T), which specific allelic variants may decrease 5-HT2AR-mediated transmission (as in Htr2a(-/-)mice), were studied in a sample of 485 Caucasian patients with MDD.
A total of 26 outpatients with treatment-resistant MDD and 27 matched healthy controls underwent magnetic resonance imaging and genotyping for six SNPs in monoaminergic genes [serotonin transporter (SLC6A4), norepinephrine transporter (SLC6A2), serotonin 1A and 2A receptors (HTR1A and HTR2A), catechol-O-methyltransferase (COMT), and brain-derived neurotrophic factor (BDNF)].
Additional evidence for a role of serotonin (5-HT) in the pathogenesis of suicidal behavior is provided by a recent report that the 5-HT2A (HTR2A) T102C polymorphism was associated with suicidality in patients with major depression.
The results demonstrated that the -1438G/A promoter polymorphism in the 5-HT(2A) receptor gene was unlikely to have a major role in therapeutic response to fluvoxamine in Japanese patients with major depressive disorder.
To explore the possible relationship between six single nucleotide polymorphisms (SNPs) (rs6311 and rs6305 of 5-HT2A, rs5443 of Gβ3, rs2230739 of ACDY9, rs1549870 of PDE1A and rs255163 of CREB1, which are all related with 5-HT2A the signal transduction pathway) and the response efficacy to selective serotonin reuptake inhibitor (SSRI) treatments in major depressive disorder (MDD) Chinese.
While further work is needed to identify the actual functional genetic variants involved, these results suggest that a relationship exists between genetic variation in HTR2A and either 5-HTT expression or central serotonergic transmission that influences the therapeutic response to 5-HTT inhibition in major depression.
Six polymorphisms in four genes related to the serotonin system, including the HTTLPR and HTTVNTR in the SLC6A4 gene, rs6295 in the HTR1A gene, rs11568817 and rs130058 in the HTR1B gene, and rs6313 in the HTR2A gene, were studied in 420 patients with MD to investigate the relationship between these genes and suicidal ideation in MD.
Our results suggest that the 102T/C polymorphism in 5-HT2A receptor gene is primarily associated with suicidal ideation in patients with major depression.Am.J. Med.Genet.(Neuropsychiatr.Genet.)96:56-60, 2000.