A preliminary association study between serotonin transporter (5-HTTLPR), receptor polymorphisms (5-HTR1A, 5-HTR2A) and depression symptom-clusters in a north Indian population suffering from Major Depressive Disorder (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)].
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.
Accordingly, two single nucleotide polymorphisms of the HTR2A gene (rs6314 ie His452Tyr and rs6313 ie 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.
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.
Many studies investigated the association between MDD and BD with the 5-HT2A102 T/C, the 5-HTT promoter 44 bp insertion/deletion and the intron 2 VNTR polymorphisms, and thus, these could be pooled using meta-analytic techniques.
No significant association between the 5-HTR2A gene SNP rs6311 and the risk of MDD was observed by four genetic models in the current meta-analysis (P = 0·12 for A versus G; P = 0·11 for AA versus GG; P = 0·06 for AA+AG versus GG; P = 0·24 for AG+GG versus AA).
Our results demonstrate the influence of a HTR2A polymorphism on aspects of somatization in major depression, which co-occurs with an unfavorable antidepressant treatment outcome.
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.
Our results support the hypothesis that the -1438A/G polymorphism of the promoter region of the 5-HTR2A gene is associated with MDD patients in a Korean population.
Overall our results suggest that the investigated 5-HT2A and 5-HTTLPR polymorphisms are not major susceptibility factors in the etiology of major depression.
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.