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

Abstract

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