The Interaction of TPH2 and 5-HT2A Polymorphisms on Major Depressive Disorder Susceptibility in a Chinese Han Population: A Case-Control Study.

Jiarun Yang,Zhengxue Qiao,Xiongzhao Zhu,Xiuxian Yang,Xueyan Zhao,Jingsong Ma,Yanjie Yang,Erying Zhao,Depin Cao,Bo Ban,Xiaohui Qiu

doi:10.3389/fpsyt.2019.00172

Abstract

Purpose: TPH2 and 5-HT2A appear to play vital roles in the homeostatic regulation of serotonin levels in the brain, their genetic variations may lead to impaired homeostatic regulation of serotonin resulting in abnormal levels of serotonin in the brain, thus predisposing individuals to MDD. However, research studies have yet to confirm which gene-gene interaction effect between TPH2 and 5-HT2A polymorphisms results in increased susceptibility to MDD.Methods: A total of 565 participants, consisting of 278 MDD patients and 287 healthy controls from the Chinese Han population, were recruited for the present study. Six single nucleotide polymorphisms (SNPs) of TPH2/5-HT2A were selected to assess their interaction by use of a generalized multifactor dimensionality reduction method.Results: A-allele carriers of rs11178997 and rs120074175 were more likely to suffer from MDD than T-allele carriers of rs11178997, or G-allele carriers of rs120074175. The interaction between TPH2 (rs120074175, rs11178997) and 5-HT2A (rs7997012) was considered as the best multi-locus model upon the MDD susceptibility.Conclusions: Our data identified an important effect of TPH2 genetic variants (rs11178997 and rs120074175) upon the risk of MDD, and suggested that the interaction of TPH2/5-HT2A polymorphism variants confer a greater susceptibility to MDD in Chinese Han population.

Highlights

Major depressive disorder (MDD) is a frequently occurring mental disorder with a strikingly high rate of relapses, and has become the leading cause of years lived with disability worldwide according to data compiled by the World Health Organization
Aberrant genes are known to predispose subjects to depression [31], the validation of MDD susceptibility genes, including tryptophan hydroxylase-2 (TPH2) and 5-HT2A, its interaction is unclear leading to the need for further investigations of the potential gene-gene interaction effects played by the key regulators of serotonin system in MDD susceptibility
The results of the present study suggested the important effect of the TPH2 gene upon the risk of MDD, and provided preliminary evidence that the interaction between TPH2 and 5-HT2A polymorphism variants may influence MDD susceptibility

Summary

Introduction

Major depressive disorder (MDD) is a frequently occurring mental disorder with a strikingly high rate of relapses, and has become the leading cause of years lived with disability worldwide according to data compiled by the World Health Organization. Rs120074175 (1463G/A), a functional polymorphism variant of TPH2, which was shown to attenuate the synthesis of serotonin by ∼80%, was associated with MDD [8]. The association of MDD and a haplotype block including rs4570625 and rs11178997 (473T/A) was confirmed [12]. These findings strongly indicated that TPH2 polymorphisms may play an important role in the development of MDD. In spite of the fact that TPH2 polymorphisms could result in the attenuation of serotonin synthesis, the genetic variation of TPH2 in isolation is unlikely to lead to a high risk of MDD [13, 14]

Objectives

Methods

Results

Conclusion