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

Katarzyna Bialek; Piotr Czarny; Cezary Watala; Paulina Wigner; Monika Talarowska; Piotr Galecki; Janusz Szemraj; Tomasz Sliwinski

doi:10.7717/peerj.8676

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

PeerJ. 2020 Feb 25:8:e8676. doi: 10.7717/peerj.8676. eCollection 2020.

Authors

Katarzyna Bialek¹, Piotr Czarny², Cezary Watala³, Paulina Wigner¹, Monika Talarowska⁴, Piotr Galecki⁵, Janusz Szemraj², Tomasz Sliwinski¹

Affiliations

¹ Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
² Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.
³ Department of Haemostatic Disorders, Medical University of Lodz, Lodz, Poland.
⁴ Institute of Psychology, Department of Personality and Individual Differences, University of Lodz, Lodz, Poland.
⁵ Department of Adult Psychiatry, Medical University of Lodz, Lodz, Poland.

Abstract

Background: 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-TGFB1 (rs1800469), g.132484229C>A-IRF (rs2070729), g.186643058A>G-PTGS2 (rs5275), g.186640617C>T-PTGS2 (rs4648308), g.70677994G>A-TGFA (rs2166975) and g.42140549G>T-IKBKB (rs5029748).

Methods: A total of 360 (180 patients and 180 controls) DNA samples were genotyped using TaqMan probes.

Results: We observed that A/G of the rs2166975 TGFA, A/C of rs2070729 IRF1 and G/T of rs5029748 IKBKB were associated with an increased risk of depression development while the T/T of rs5029748 IKBKB, T/T of rs4648308 PTGS2 and G/G of rs2166975 TGFA reduced this risk. We also stratified the study group according to gender and found that genotype A/G and allele G of the rs2166975 TGFA, G/T of rs5029748 IKBKB as well as C allele of rs4648308 PTGS2, homozygote A/A and allele A of rs5275 PTGS2 were associated with increased risk of depression development in men while homozygote G/G of rs5275 PTGS2 decreased this risk. Moreover, C/T of rs4648308 PTGS2 and A/G of rs5275 PTGS2 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 TGFB1 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 IRF1 and T/T of rs5029748 IKBKB 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.

Keywords: Cytokines; Depression; Inflammation; Major depressive disorder; Single nucleotide polymorphism.

Grants and funding

This study was supported by funding from a scientific research grant from the Polish National Science Centre (No. UMO-2015/19/BNZ7/00410). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.