SOD2 genetic polymorphism (rs4880) has no impact on 6‐month response to antidepressant treatment and inflammatory biomarkers in depressed patients

Abstract

Two thirds of patients suffering from a major depressive episode (MDE) do not reach a complete response with antidepressant drugs. This lack of response is due to several factors, including genetic determinants. Since major depressive disorder is associated with inflammatory and oxidative stress abnormalities, the metabolism of superoxide anions might be involved in non‐response to antidepressant drugs. Superoxide anions are metabolized by manganese‐dependent superoxide dismutase (SOD2) in the mitochondria. A functional genetic polymorphism (SOD2, rs4880), responsible of a 40% reduction in enzyme activity, is associated with anti‐inflammatory response of rosuvastatin. We investigated the association of ala‐allele of SOD2 rs4880 and both antidepressant efficacy and inflammatory parameters in patients treated for a MDE with antidepressant drugs. The Hamilton Depression Rating Scale (HDRS) score and levels of plasma CRP and inflammatory cytokines were assessed at baseline, one month (M1), 3 months (M3) and 6 months (M6) after antidepressant treatment. They were compared according to SOD2 genetic polymorphism. Of the 484 patients studied, 361 (74.6%) carried the ala‐allele (Ala group), 123 (25.4%) of them had Val/Val genotype (Val/Val group). No significant difference was observed between the Ala and Val/Val groups neither for baseline clinical characteristics, nor for HDRS scores, response/remission rates, plasma CRP and cytokine levels throughout the study. The rs4880 SOD2 genetic polymorphism was not associated with the clinical response and cytokines levels after antidepressant treatment. These data suggest that SOD2 is not a major genetic determinant of antidepressant response. Other genes of the oxidative stress pathways should be explored in further studies.

Oxidative Stress Markers and Antioxidant Enzymes in Children and Adolescents with Depressive Disorder and Impact of Omega-3 Fatty Acids in Randomised Clinical Trial

“…Mitochondrial SOD polymorphism (SOD2) has been found to increase the risk of depression in the elderly [ 43 ]. On the other hand, the SOD2 polymorphism rs4880 has no effect on the antidepressant response and inflammatory markers [ 44 ]. The influence of the paraoxonase 1 (PON1) polymorphisms, which affect the formation of ROS/RNS and the immuno-inflammatory characteristics of depression, has also been discussed [ 45 , 46 ].…”

Major Depressive Disorder and Oxidative Stress: A Review of Peripheral and Genetic Biomarkers According to Clinical Characteristics and Disease Stages

“…Second, antioxidant enzymes were largely explored. Superoxide dismutases (SODs) are the first and main protective barrier against oxidative stress [ 87 , 88 ]. These enzymes catalyze the dismutation reaction of O 2 − (principally produced by the mitochondrial respiratory chain) in H 2 O 2 [ 88 ].…”

“…For MnSOD, similar results were found [ 91 , 93 ]. Concerning genetic polymorphisms, the SOD2 Val16Ala polymorphism (rs4880) was described to be associated with MDD prevalence [ 87 ]. In two studies, the Ala16 allele seemed to be a protective factor in MDD [ 80 , 85 ].…”

Genetic profile for the detection of susceptibility to poisoning by exposure to pesticides

“…However, some enzymes with antioxidant activity can neutralize these free radicals, although antioxidant enzymes may have variants or polymorphisms that alter their activities [4,46]. The superoxide dismutase (SOD2) gene neutralizes superoxide anion produced in the mitochondrial respiratory chain [47,48]. The enzyme NAD(P)H quinone oxidoreductase 1 (NQO1) gene is responsible for reducing free radicals from pesticide that produce residues with quinone structures [3,49].…”

“…It encodes the enzyme manganese superoxide dismutase (MnSOD or SOD2), a homotetramer with a manganese ion (Mn 2+ / Mn 3+ ) as a cofactor in each subunit [29,48]. SOD2 is an antioxidant enzyme in the mitochondrial matrix that catalyzes the dismutation of the mitochondrial superoxide anion into hydrogen peroxide and oxygen; in addition, it is involved in the regulation of apoptosis in tumors [47,51,52]. SOD2 is highly polymorphic, where the SNP rs4880 (exon 2, Ala16Val; 47C> T) is of medical importance [45,50,52,53].…”