Epigenetic variation at the SLC6A4 gene promoter in mother-child pairs with major depressive disorder.

Background: Genetic and epigenetic variations of the serotonin transporter gene (SLC6A4) have been related to the etiology of depression. The 5-HTTLPR polymorphism at the SLC6A4 promoter region has two variants, a short allele (S) and a long allele (L), in which the S allele results in lower gene transcription and has been associated with depression. The short S-allele of 5-HTTLPR polymorphism of this gene has been associated with depression. In addition to molecular mechanisms, exposure to early life risk factors such as maternal depression seems to affect the development of depression in postnatal life. The present study investigated the association of 5-HTTLPR polymorphism and CpG DNA methylation (5mC) levels of an AluJb repeat element at the SLC6A4 promoter region in mother-child pairs exposed to maternal depression.

Methods: We analyzed DNA samples from 60 subjects (30 mother-child pairs) split into three groups, with and without major depression disorder (DSM-IV) among children and mothers. The genotyping of 5-HTTLPR polymorphism and quantification of 5mC levels was performed by qualitative PCR and methylation-sensitive restriction enzyme digestion, and real-time quantitative PCR (MSRED-qPCR), respectively.

Results: The sample analyzed presented a higher frequency of S allele of 5-HTTLPR (67.5%). Despite the high frequency of this allele, we did not find statistically significant differences between individuals carrying at least one S allele between the depression and healthy control subjects, or among the mother-child pair groups with different patterns of occurrence of depression. In the group where the mother and child were both diagnosed with depression, we found a statistically significant decrease of the 5mC level at the SLC6A4 promoter region.

Limitations: The limitations are the relatively small sample size and lack of gene expression data available for comparison with methylation data.

Conclusion: In this study, we demonstrated a repeat element specific 5mC level reduction in mother-child pairs, concordant for the diagnosis of depression.