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Front Psychiatry. 2019 Apr 4;10:172. doi: 10.3389/fpsyt.2019.00172. eCollection 2019.

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

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Department of Medical Psychology, Institute of Public Health, Harbin Medical University, Harbin, China.
Department of Endocrinology, Affiliated Hosptial of Jining Medical University, Jining, China.
Medical Psychological, Institute of the Second Xiangya Hospital of Central South University, Changsha, China.
Department of Medical Education Management, Harbin Medical University, Harbin, China.


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.


5-HT2A; TPH2; gene-gene interaction; major depressive disorder; polymorphisms

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