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

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.