Jingsong Ma1, Hai Xiao2, Yanjie Yang3, Depin Cao4, Lin Wang1, Xiuxian Yang1, Xiaohui Qiu1, Zhengxue Qiao1, Junyao Song1, Yuexi Liu1, Peng Wang1, Jiawei Zhou1, Xiongzhao Zhu5. 1. Psychology Department of the Public Health Institute of Harbin Medical University, Heilongjiang Province, China. 2. Harbin Medical University, Heilongjiang Province, China. 3. Psychology Department of the Public Health Institute of Harbin Medical University, Heilongjiang Province, China. Electronic address: yanjie1965@163.com. 4. Harbin Medical University, Heilongjiang Province, China. Electronic address: caodp211@163.com. 5. Medical Psychological Institute of the Second Xiang Ya Hospital of Central South University, Hunan Province, China.
Abstract
BACKGROUND: Major depression (MD) results from a complex synergy between genetic and environmental factors. The aim of this study is to analyze the interaction of tryptophan hydroxylase 2 gene (TPH2) variation and negative life events in the pathogenesis of MD. Three TPH2 polymorphisms, -703G/T (rs4570625), -473T/A (rs11178997), and 1463G/A (rs120074175), were selected based on previous findings of associations with MD. METHODS: In this study, 289 patients with MD and 289 age- and sex-matched control subjects were genotyped. The frequency and severity of negative life events were assessed by the Life Events Scale (LES). Gene-environment interactions (G×E) were assessed using the generalized multifactor dimensionality reduction (GMDR) method. RESULTS: Differences in rs11178997 and rs120074175 allele frequencies and genotype distributions were observed between MD patients and controls. Significant G×E interactions between negative life events and allelic variation of rs4570625, rs11178997, and rs120074175 were also observed. Individuals carrying the T(-) genotype of rs4570625 (GG), T(-) genotype of rs11178997 (AA), or A(-) genotype of rs120074175 (GG) were susceptible to MD only when exposed to high-negative life events. However, individuals with the T(+) genotypes of rs11178997 (TA, TT) and A(+) genotypes of rs120074175 (AG, AA) were susceptible to MD when exposed to low-negative life events. LIMITATION: Assessment of negative life events was influenced by subjective interpretation. CONCLUSIONS: Interactions between multiple TPH2 gene alleles and negative life events were revealed by GMDR analysis. Chinese Han individuals with at least one rs11178997 T allele or rs120074175 A allele are susceptible to MD even in the relative absence of high-negative life events.
BACKGROUND: Major depression (MD) results from a complex synergy between genetic and environmental factors. The aim of this study is to analyze the interaction of tryptophan hydroxylase 2 gene (TPH2) variation and negative life events in the pathogenesis of MD. Three TPH2 polymorphisms, -703G/T (rs4570625), -473T/A (rs11178997), and 1463G/A (rs120074175), were selected based on previous findings of associations with MD. METHODS: In this study, 289 patients with MD and 289 age- and sex-matched control subjects were genotyped. The frequency and severity of negative life events were assessed by the Life Events Scale (LES). Gene-environment interactions (G×E) were assessed using the generalized multifactor dimensionality reduction (GMDR) method. RESULTS: Differences in rs11178997 and rs120074175 allele frequencies and genotype distributions were observed between MD patients and controls. Significant G×E interactions between negative life events and allelic variation of rs4570625, rs11178997, and rs120074175 were also observed. Individuals carrying the T(-) genotype of rs4570625 (GG), T(-) genotype of rs11178997 (AA), or A(-) genotype of rs120074175 (GG) were susceptible to MD only when exposed to high-negative life events. However, individuals with the T(+) genotypes of rs11178997 (TA, TT) and A(+) genotypes of rs120074175 (AG, AA) were susceptible to MD when exposed to low-negative life events. LIMITATION: Assessment of negative life events was influenced by subjective interpretation. CONCLUSIONS: Interactions between multiple TPH2 gene alleles and negative life events were revealed by GMDR analysis. Chinese Han individuals with at least one rs11178997 T allele or rs120074175 A allele are susceptible to MD even in the relative absence of high-negative life events.
Authors: Paulina Wigner; Piotr Czarny; Ewelina Synowiec; Michał Bijak; Katarzyna Białek; Monika Talarowska; Piotr Galecki; Janusz Szemraj; Tomasz Sliwinski Journal: J Cell Mol Med Date: 2018-01-05 Impact factor: 5.310
Authors: Gabriel Rodrigues Coutinho Pereira; Gustavo Duarte Bocayuva Tavares; Marta Costa de Freitas; Joelma Freire De Mesquita Journal: PLoS One Date: 2020-03-02 Impact factor: 3.240