Novel association between TGFA, TGFB1, IRF1, PTGS2 and IKBKB single-nucleotide polymorphisms and occurrence, severity and treatment response of major depressive disorder

• Published in: PeerJ (San Francisco, CA) Vol. 8; p. e8676
• Main Authors: Bialek, Katarzyna, Czarny, Piotr, Watala, Cezary, Wigner, Paulina, Talarowska, Monika, Galecki, Piotr, Szemraj, Janusz, Sliwinski, Tomasz
• Format: Journal Article
• Language: English
• Published: United States PeerJ, Inc 25.02.2020; PeerJ Inc
• Subjects: Alleles; Cell adhesion & migration; Cytokines; Depression; Disease; DNA probes; Experiments; Gene expression; Genetics; Growth factors; Immune system; Inflammation; Interferon regulatory factor 1; Kinases; Major depressive disorder; Medical Genetics; Mental depression; Nervous system; Pathogenesis; Pharmacology; Proteins; Psychiatry and Psychology; Serotonin uptake inhibitors; Single nucleotide polymorphism; Transcription factors; Transforming growth factor-b1; Tumor necrosis factor-TNF; Depression; Inflammation; Single nucleotide polymorphism; Cytokines; Major depressive disorder
• ISSN: 2167-8359; 2167-8359
• DOI: 10.7717/peerj.8676

Activation of the immune system might affect the severity of depressive episodes as well as response to the antidepressant treatment. The purpose of this study was to investigate whether the occurrence of variant alleles of analyzed SNPs are involved in prevalence and progression of depression. Moreover, selected genes and SNPs have not been investigated in context of the disease severity and treatment. Therefore, six polymorphisms were selected: g.41354391A>G- (rs1800469), g.132484229C>A- (rs2070729), g.186643058A>G- (rs5275), g.186640617C>T- (rs4648308), g.70677994G>A- (rs2166975) and g.42140549G>T- (rs5029748). A total of 360 (180 patients and 180 controls) DNA samples were genotyped using TaqMan probes. We observed that A/G of the rs2166975 , A/C of rs2070729 and G/T of rs5029748 were associated with an increased risk of depression development while the T/T of rs5029748 , T/T of rs4648308 and G/G of rs2166975 reduced this risk. We also stratified the study group according to gender and found that genotype A/G and allele G of the rs2166975 , G/T of rs5029748 as well as C allele of rs4648308 , homozygote A/A and allele A of rs5275 were associated with increased risk of depression development in men while homozygote G/G of rs5275 decreased this risk. Moreover, C/T of rs4648308 and A/G of rs5275 was positively correlated with the risk of the disease occurrence in women. Furthermore, a gene-gene analysis revealed a link between studied polymorphisms and depression. In addition, A/A of rs1800469 was associated with earlier age of onset of the disease while G/G of this SNP increased severity of the depressive episode. Interestingly, A/C of rs2070729 and T/T of rs5029748 may modulate the effectiveness of selective serotonin reuptake inhibitors therapy. In conclusion, studied SNPs may modulate the risk of occurrence, age of onset, severity of the disease and response to the antidepressant treatment.