Genetic Polymorphisms Modifying Oxidative Stress Are Associated with Disease Activity in Rheumatoid Arthritis Patients

Abstract

Abstract.Reactive oxygen and nitrogen species are involved in the pathology of rheumatoid arthritis (RA). Polymorphisms in genes coding for superoxide dismutases (SOD2 and SOD3), catalase (CAT), tumor necrosis factor-alpha (TNFA) and inducible NO synthase (NOS2A) may influence RA activity. We determined SOD2 Ala-9Val, SOD3 Arg213Gly, CAT C-262T, TNFA G-308A, TNFA C-857T and NOS2A (CCTTT)n polymorphisms in 327 RA patients. Carriers of CAT -262T and TNFA -308A allele had lower mean disease activity score of 28 joint count (DAS28) values than patients with CAT -262CC and TNFA -308GG genotypes (p = 0.014 and p = 0.046, respectively). Patients with the combination of CAT -262T and TNFA -308A allele had lower mean DAS28 values and a higher probability for low disease activity than non-carriers (p = 0.003, OR = 3.585, 95% CI = 1.538-8.357). Our results suggest that CAT and TNFA polymorphisms alone and in combination influence the activity of RA.

Gene Polymorphisms of Tumor Necrosis Factor Alpha and Antioxidant Enzymes in Bronchial Asthma

“…Superoxide dismutase (SOD) catalyses the dismutation of O 2 ⋅ -to H 2 O 2 and oxygen (O 2 ), while catalase (CAT) decomposes H 2 O 2 to water and oxygen. Single nucleotide polymorphisms (SNPs) of genes coding the antioxidant enzymes may alter enzyme structure, substrate specificity or activity and thus modify inter-individual variability in the defense capacity against oxidative stress [4]. The most extensively studied rs4880 (MnSOD Ala16Val) polymorphism of the manganese superoxide dismutase (MnSOD) gene is located at amino acid position 16 in the mitochondrial targeting sequence (MTS) resulting in the replacement of an alanine with a valine (Ala16Val).…”

A Possible Relationship Between Polymorphisms of Glutathione S-Transferase M1, P1 and T1 Genes and Rheumatoid Arthritis in Zahedan, Southeast Iran

“…In contrast, Bohanec et al [14] provided evidence that patients with the GSTT1 null genotype had a higher risk for developing high activity RA than patients with GSTT1 genes present and that the GSTM1 and GSTP1 polymorphisms were not associated with the disease activity.…”

Genetic Polymorphism of C-262T Catalase and Susceptibility to Schizophrenia

“…At present we know that chronic exposure to excess ROS may contribute to brain damage and pathophysiology of schizophrenia [1,2,11,12], CAT involved in detoxification of ROS [5][6][7][8][9][10], and C-262T polymorphism is associated with CAT activity [3,4]. Taken together, these findings sufficiently provide us with a theoretical ration to investigate the association between CAT C-262T polymorphism and susceptibility to schizophrenia.…”

“…Several studies indicated that the polymorphism of C-262T CAT is associated with some multifactorial diseases [5][6][7][8][9][10]. At present we know that chronic exposure to excess ROS may contribute to brain damage and pathophysiology of schizophrenia [1,2,11,12], CAT involved in detoxification of ROS [5][6][7][8][9][10], and C-262T polymorphism is associated with CAT activity [3,4].…”