Relationship between G1287A of the NET Gene Polymorphisms and Brain Volume in Major Depressive Disorder: A Voxel-Based MRI Study

PLoS One. 2016 Mar 9;11(3):e0150712. doi: 10.1371/journal.pone.0150712. eCollection 2016.

Abstract

Background: Earlier studies implicated norepinephrine transporter (NET) gene (SLC6A2) polymorphisms in the etiology of major depressive disorder (MDD). Recently, two single nucleotide SLC6A2 polymorphisms, G1287A in exon 9 and T-182C in the promoter region, were found to be associated with MDD in different populations. We investigated the relationship between the brain volume and these two polymorphisms of the SLC6A2 in MDD patients.

Methods: We obtained 3D high-resolution T1-weighted images of 30 first-episode MDD patients and 48 age- and sex-matched healthy subjects (HS). All were divided into 4 groups based on polymorphism of either the G1287A or the T-182C genotype. VBM analysis examined the effects of diagnosis, genotype, and genotype-diagnosis interactions.

Results: Diagnosis effects on the brain morphology were found in the left superior temporal cortex. No significant genotype effects were found in the T-182C and the G1287A. A significant genotype (G1287A)-diagnosis interaction was found in the left dorsolateral prefrontal cortex. No significant genotype (T-182C)-diagnosis interaction effects were observed in any brain region.

Conclusions: In MDD patients there seems to be a relationship between the volume of the dorsolateral prefrontal cortex and polymorphism of the SLC6A2 G1287A gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / pathology*
  • Demography
  • Depressive Disorder, Major / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Norepinephrine Plasma Membrane Transport Proteins / genetics*
  • Organ Size
  • Polymorphism, Single Nucleotide / genetics*

Substances

  • Norepinephrine Plasma Membrane Transport Proteins
  • SLC6A2 protein, human

Grants and funding

This work received technical support from Scientific Research on Innovative Areas (Comprehensive Brain Science Network) from the Ministry of Education, Science, Sports, and Culture of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.