Genetic Role of BDNF Val66Met and 5-HTTLPR Polymorphisms on Depressive Disorder

Abstract

ObjectiveWe investigated possible association between depressive disorders and BDNF Val66Met and 5-HTTLPR. Brain derived neurotrophic factor (BDNF) gene and serotonin transporter (SLC6A4) gene are promising candidate genes for depressive disorders. It has been suggested that BDNF promotes the survival and differentiation of serotonergic neurons and that serotonergic transmission exerts powerful control over BDNF gene expression.MethodsFinal analyses were performed on 186 patients with depressive disorders and 1032 controls. Val66Met polymorphism of BDNF gene and 5-HTTLPR polymorphism of serotonin transporter gene were genotyped and allele and genotypic associations on the diagnosis of depression and age at onset of depression were analyzed.ResultsThe 5-HTTLPR was positively associated with depressive affected status in the total sample and in females (p=0.038 for allelewise, p=0.015 for genotype-wise associations), but, not in males. The BDNF Val66Met showed no association with depression. BDNF Val66Met and 5-HTTLPR alone were not associated with age at onset of depression. Additional analysis on the interaction between BDNF Val66Met and 5-HTTLPR found a significant association with age at onset of depression in the entire patient group. This association was also found in the female but not in the male patient group. None of the positive results survived Bonferroni correction for multiple testing.ConclusionThis result suggested that BDNF Val66Met and 5-HTTLPR may contribute to depressive disorders in a complex way and that the genetic effect could differ by gender. Further studies with large number of patients will be necessary.

Polymorphism in the promoter of the gene for the serotonin transporter affects the age of onset of major depressive disorder in the Japanese population

“…Although a previous study showed a positive influence of the interaction between 5HTTLPR and a Val66Met substitution in brain-derived neurotropic factor on the age of onset of depressive disorder in the Korean population (Lee et al, 2014), ours is the first study showing a significant dose-dependent relationship between 5HTTLPR and the age of onset of MDD.…”

Influence of childhood trauma and brain-derived neurotrophic factor Val66Met polymorphism on posttraumatic stress symptoms and cortical thickness

“…Another possible reason behind the mixed results related to the genotype effect may be gene-gene interaction. A few studies suggested in fact that the BDNF genotype may interact with the catechol O-methyltransferase (COMT) and the serotonin transporter gene linked promoter region (5-HTTLPR) to produce differences in resilience 74 and onset age of depressive disorder 75 , respectively. Further studies investigating such a gene-gene interaction are needed, given that PTSD is known to be related to resilience 76 , depression 77 , and other psychological factors.…”

Genetic epidemiology of migraine and depression

“…Previous studies have reported both positive and negative results regarding the association between 5-HTTLPR and migraine/depression susceptibility (42–47). In terms of migraine, for instance, Juhasz et al.…”

“…A positive association was also identified from a recent meta-analysis (43) that showed that 5-HTTLPR was significantly associated with European female migraineurs carrying the s allele (OR: 2.02; 95% CI: 1.24–3.28). In terms of depression, a recent Korean study (44) detected that both the s allele and genotype frequencies of 5-HTTLPR were significantly associated with depression (adjusted p -value = 0.050 for allelic association; adjusted p -value = 0.015 for genotypic association). In a haplotype analysis (45), a significant association was reported between the 5-HTTLPR TA haplotype (tagging s allele) and MDD (OR: 1.14; 95% CI: 1.04–1.25).…”