The Combined Effects of the 5-HTTLPR and 5-HTR1A Genes Modulates the Relationship Between Negative Life Events and Major Depressive Disorder in a Chinese Population

Background: Serotonin transporter (5-HTT) and 5-HT receptor (5-HTR) involved in the neurotransmission of 5-HT may play an important role in the development of major depression disorder (MDD). Several lines of evidence suggested that the gene-environment interaction may confer susceptibility to depression. The aim of this study is to analyze the combined effect of four serotonin-related genes and two environmental factors on MDD in a Chinese population.

Methods: This study recruited a total of 401 patients with MDD and 391 age- and gender-matched control subjects. They were all Chinese Han origin. Negative life events and objective social supports were assessed using standard rating scales. Six polymorphisms in the four serotonin-related genes (5-HTT, 5-HTR1A, 5-HTR1B and 5-HTR2A) were selected to detect. The analyses of the gene-environment interactions were performed by the Multifactor Dimensionality Reduction (MDR).

Results: Allelic associations between patients with MDD and controls were observed for the polymorphism of 5-HTTLPR and for rs6295 at the 5-HTR1A locus. The 5-HTTLPR polymorphism was associated with negative life events on MDD. A three-way interaction between the 5-HTTLPR polymorphism, rs6295 and negative life events on MDD was found in the individuals aged from 20 years to 29 years. In addition, the individuals carrying the L/L genotype of 5-HTTLPR could be susceptible to MDD when exposed to negative life events.

Conclusions: The 5-HTTLPR polymorphism may modify the interaction between negative life events and MDD in the Chinese population. To our knowledge, this is the first report on the combined effect for the 5-HTTLPR polymorphism and 5-HTR1A genes on modifying the response to negative life events conferring susceptibility to MDD in the 20-29 year group.