A molecular validation of serotonin signaling systems association with major depressive disorder (MDD) in South Indian population

Abstract

Major depressive disorder (MDD) is a multi factorial disease that affects morbidity, mortality and quality of life. It is chronic and recurrent phenotype of complex etiological relationship between genetic and environmental factors. The serotonergic system plays an important role in the modulation of brain function. Tryptophan hydroxylase (TPH) converts tryptophan in the brain to 5‐hydroxytryptophan (5‐HTP). TPH is the rate‐limiting enzyme in 5‐HT synthesis. Most tissues synthesize 5‐HT, a relatively unstable substance at low levels. Minor changes in TPH abundance or the activity can dramatically alter 5‐HT content and serotonergic function. With regard to MDD, there is a strong evidence for serotonergic abnormalities. The present study was performed to validate the association of single nucleotide polymorphisms (SNPs) in several functional variants of serotonergic genes [serotonin‐transporter‐linked polymorphic region (5HTTLPR), TPH1 and TPH2] with MDD in South Indian population. We have analyzed genotypic polymorphism in well characterized sample of MDD patients and controls with PCR‐RFLP methods. We identified a significant difference in the frequency of 5HTTLPR, TPH1 and TPH2 gene alleles between patients and controls. In addition, there was a significant difference in genotypic distribution of 5HTTLPR and TPH2 alleles between these two groups. The distribution of 5HTTLPR genotype frequencies SS, SL, LL and TPH2 GG, TT, GT and SS, GG allele showed strong association with MDD. To our knowledge, the present study reveals for the first time that polymorphism in 5HTTLPR and TPH2 genes may play a role in susceptibility to MDD in South Indian population.Support or Funding InformationThis work was supported by research grant from the Karpagam Research Foundation, Karpagam Faculty of Medical Sciences and Research, Coimbatore, India.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.