Yang Jiarun, Zhao Xueyan, Ma Jingsong, Qiao Zhengxue, Yang Xiuxian, Zhao Erying, Ban Bo, Zhu Xiongzhao, Cao Depin, Yang Yanjie, Qiu Xiaohui
Department of Medical Psychology, Institute of Public Health, Harbin Medical University, Harbin, China.
Department of Endocrinology, Affiliated Hosptial of Jining Medical University, Jining, China.
Front Psychiatry. 2019 Apr 4;10:172. doi: 10.3389/fpsyt.2019.00172. eCollection 2019.
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. 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. 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. 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.
色氨酸羟化酶2（TPH2）和5-羟色胺2A受体（5-HT2A）似乎在大脑血清素水平的稳态调节中发挥着至关重要的作用，它们的基因变异可能导致血清素稳态调节受损，从而导致大脑中血清素水平异常，进而使个体易患重度抑郁症（MDD）。然而，研究尚未证实TPH2和5-HT2A基因多态性之间的哪种基因-基因相互作用效应会导致对MDD的易感性增加。本研究共招募了565名参与者，其中包括278名来自中国汉族人群的MDD患者和287名健康对照。选择TPH2/5-HT2A的六个单核苷酸多态性（SNP），采用广义多因素降维法评估它们之间的相互作用。rs11178997和rs120074175的A等位基因携带者比rs11178997的T等位基因携带者或rs120074175的G等位基因携带者更易患MDD。TPH2（rs120074175，rs11178997）和5-HT2A（rs7997012）之间的相互作用被认为是MDD易感性的最佳多位点模型。我们的数据确定了TPH2基因变异（rs11178997和rs120074175）对MDD风险的重要影响，并表明TPH2/5-HT2A多态性变异的相互作用使中国汉族人群对MDD的易感性更高。
