Interaction of tryptophan hydroxylase 2 gene and life events in susceptibility to major depression in a Chinese Han population

Abstract

BackgroundMajor 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. MethodsIn 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. ResultsDifferences 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. LimitationAssessment of negative life events was influenced by subjective interpretation. ConclusionsInteractions 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.