Dataset Information

Increased serum levels of sortilin are associated with depression and correlated with BDNF and VEGF.

ABSTRACT: Neurotrophic factors have been investigated in relation to depression. The aim of the present study was to widen this focus to sortilin, a receptor involved in neurotrophic signalling. The serum sortilin level was investigated in 152 individuals with depression and 216 control individuals, and eight genetic markers located within the SORT1 gene were successfully analysed for association with depression. Genotyping was performed using the Sequenom MassARRAY platform. All the individuals returned a questionnaire and participated in a semi-structured diagnostic interview. Sortilin levels were measured by immunoassay, and potential determinants of the serum sortilin level were assessed by generalized linear models. Serum levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were measured in previous studies. We identified a significant increase of serum sortilin levels in depressed individuals compared with controls (P=0.0002) and significant positive correlation between serum sortilin levels and the corresponding levels of BDNF and VEGF. None of the genotyped SNPs were associated with depression. Additional analyses showed that the serum sortilin level was influenced by several other factors. Alcohol intake and body mass index, as well as depression, serum BDNF and serum VEGF were identified as predictors of serum sortilin levels in our final multivariate model. In conclusion, the results suggest a role of circulating sortilin in depression which may relate to altered activity of neurotrophic factors.

SUBMITTER: Buttenschon HN

PROVIDER: S-EPMC5068760 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Increased serum levels of sortilin are associated with depression and correlated with BDNF and VEGF.

Buttenschøn H N HN Demontis D D Kaas M M Elfving B B Mølgaard S S Gustafsen C C Kaerlev L L Petersen C M CM Børglum A D AD Mors O O Glerup S S

Translational psychiatry 20151110

Neurotrophic factors have been investigated in relation to depression. The aim of the present study was to widen this focus to sortilin, a receptor involved in neurotrophic signalling. The serum sortilin level was investigated in 152 individuals with depression and 216 control individuals, and eight genetic markers located within the SORT1 gene were successfully analysed for association with depression. Genotyping was performed using the Sequenom MassARRAY platform. All the individuals returned ...[more]

PMID: 26556286

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Project description:BackgroundBrain-derived neurotrophic factor is implicated in the pathophysiology of major depressive disorder and suicide. Both are partly caused by early life adversity, which reduces brain-derived neurotrophic factor protein levels. This study examines the association of brain-derived neurotrophic factor Val66Met polymorphism and brain brain-derived neurotrophic factor levels with depression and suicide. We hypothesized that both major depressive disorder and early life adversity would be associated with the Met allele and lower brain brain-derived neurotrophic factor levels. Such an association would be consistent with low brain-derived neurotrophic factor mediating the effect of early life adversity on adulthood suicide and major depressive disorder.MethodsBrain-derived neurotrophic factor Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 nonsuicides. Additionally, brain-derived neurotrophic factor protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9), anterior cingulate cortex (Brodmann area 24), caudal brainstem, and rostral brainstem. The relationships between these measures and major depressive disorder, death by suicide, and reported early life adversity were examined.ResultsSubjects with the Met allele had an increased risk for depression. Depressed patients also have lower brain-derived neurotrophic factor levels in anterior cingulate cortex and caudal brainstem compared with nondepressed subjects. No effect of history of suicide death or early life adversity was observed with genotype, but lower brain-derived neurotrophic factor levels in the anterior cingulate cortex were found in subjects who had been exposed to early life adversity and/or died by suicide compared with nonsuicide decedents and no reported early life adversity.ConclusionsThis study provides further evidence implicating low brain brain-derived neurotrophic factor and the brain-derived neurotrophic factor Met allele in major depression risk. Future studies should seek to determine how altered brain-derived neurotrophic factor expression contributes to depression and suicide.

Project description:Rheumatoid arthritis (RA) is one of the chronic autoimmune diseases, with genetic and environmental predisposition, and synovial angiogenesis is considered to be a notable stage in its pathogenesis. Angiogenesis or vascular proliferation has been suggested to be a pivotal mechanism involved in both inflammation/immune activation and joint invasion and destruction. RA may be considered an "angiogenic disease" because it is associated with active tissue neovascularization. Vascular endothelial growth factor (VEGF) promotes vascular permeability, regulates angiogenesis, endothelial cell proliferation and migration, chemotaxis, and capillary hyper permeability and therefore is involved in the development of inflammation. VEGF is the most potent proangiogenic molecule promoting the angiogenic phenotype of RA and is upregulated in RA.The aim of the study was to identify functional VEGF variants and their possible association with VEGF expression, susceptibility to and severity of RA.581 RA patients and of 341 healthy individuals were examined for -1154 A/G, -2578 A/C VEGF gene polymorphisms by PCR-RFLP method and for -634 G/C VEGF gene polymorphisms by TaqMan SNP genotyping assay. Serum VEGF levels in RA patients and controls were measured by ELISA.The -1154 A/G VEGF gene polymorphism under the codominant, recessive (AA+AG vs. GG) and dominant (AA vs. AG+GG) models were associated with RA (p = 0.0009; p = 0.004; p = 0.017, respectively). VEGF -2578 A/C revealed differences in the case-control distribution in codominant, recessive, dominant and overdominant models (all p<0.0001). Furthermore, the -634 G/C VEGF gene SNP was not correlated with susceptibility to RA in Polish population. The genotype-phenotype analysis showed significant association between the VEGF -1154 A/G and -634 G/C and mean value of the hemoglobin (all p = 0.05), additionally they relevated that the number of women with the polymorphic allele -2578 C was lower than the number of women with wild type allele -2578A (p = 0.006). Serum VEGF levels were significantly higher in RA patients than in control groups (both p = 0,0001).Present findings indicated that VEGF genetic polymorphism as well as VEGF protein levels may be associated with the susceptibility to RA in the Polish population.

Dataset Information

Increased serum levels of sortilin are associated with depression and correlated with BDNF and VEGF.

Publications

Increased serum levels of sortilin are associated with depression and correlated with BDNF and VEGF.

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