Effects of polymorphisms of serotonin transporter promoter (5-HTTLPR) and brain derived neurotrophic factor gene (G196A rs6265) on the risk of major depressive disorder in the Chinese Han population.

OBJECTIVE: The etiology of Major depressive disorder (MDD) is multifactorial but the genetic risk is an important factor. Previous studies have shown a significant interaction between serotonin and brain-derived neurotrophic factor (BDNF) in brain function. The serotonin transporter protein promoter polymorphism (5-HTTLPR) and BDNF (rs6265) are two of the most studied candidate gene polymorphisms in relation to MDD. However, the effect of 5-HTTLPR-BDNF (rs6265) interaction on MDD-risk is not consistent. PATIENTS AND METHODS: This study recruited 459 patients with MDD and 412 healthy volunteers in a Chinese Han population. Polymerase chain reaction (PCR)-based genotyping was used to detect polymorphisms. Logistic regression was applied to estimate the effect of polymorphisms of 5-HTTLPR, BDNF (rs6265), and their interaction. RESULTS: We observed a significant correlation between the heterozygous genotype of 5-HTTLPR and MDD [odds ratio (OR) = 1.42, 95% CI: 1.05~1.91; p = 0.02]. The BDNF (rs6265) polymorphism showed that there is no correlation with MDD. When interaction with BDNF was modeled, for individuals with BDNF (rs6265), genotype GG, cases in the heterozygous group had even higher odds of MDD than those in the combined homozygous group of 5-HTTLPR polymorphism (OR = 2.92, 95% CI: 1.43-5.95; p = 0.003). CONCLUSIONS: Our results suggested that 5-HTTLPR, may be associated with the susceptibility of MDD in an overdominant mode, and there may be a significant interaction between 5-HTTLPR and BDNF (rs6265) polymorphisms in relation to MDD.