The association of CAT-262C/T polymorphism with catalase activity and treatment response in juvenile idiopathic arthritis
Oxidative stress is believed to be of great importance for both the etiology and the persistence of juvenile idiopathic arthritis (JIA). The aim of this study was to investigate the association of -262C/T polymorphism of the catalase (CAT) gene with JIA, as well as to evaluate whether this polymorphism can influence plasma CAT activity and outcome in JIA patients treated with etanercept. A total of 154 subjects (60 JIA patients and 94 healthy volunteers) were screened for CAT-262C/T gene polymorphism using the polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. Plasma CAT activity was determined using the spectrophotometric method according to Goth, prior to and 12 months after anti-TNF (etanercept) therapy. Clinical outcome was assessed using the JIA ACR (American College of Rheumatology) response criteria. The genotype and allele frequency distributions of CAT-262C/T polymorphism in the patients were significantly different from those of the controls (p = 0.014, p = 0.006). The TT genotype (polymorphic homozygous) was associated with a 4.36-fold higher likelihood of having JIA (95% CI 1.545–12.323, p = 0.005) as compared to the CC genotype (wild-type). At month 12 of treatment, JIA patients, carriers of the CC genotype, showed significantly higher plasma CAT activity (p = 0.004) and achieved the JIA ACR 70 response more often (p = 0.003) than the patients, carriers of the CT/TT genotype. This is the first study implying the possible association of CAT-262C/T polymorphism with JIA. The results suggest the potential protective effect of the CC genotype, with regard to CAT activity and treatment outcome.
KeywordsCatalase CAT-262C/T polymorphism Etanercept Juvenile idiopathic arthritis
JB, JV, TJS and DP designed the study. JB and JV collected and interpreted data and wrote the initial draft of the manuscript. TJS, MD, TC, DL, GS, VM, MC and DP contributed to the data collection and interpretation and revised the manuscript critically. All authors approved the final version to be submitted for publication and agree to be accountable for all aspects of the work.
This work was financially supported by the Ministry of Education, Science, and Technological Development of the Republic of Serbia (Grant Number III41018).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent was obtained from all individual participants included in the study. All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
- 1.Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J et al (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 31(2):390–392Google Scholar
- 4.Umar S, Kumar A, Sajad M, Zargan J, Ansari M, Ahmad S et al (2013) Hesperidin inhibits collagen-induced arthritis possibly through suppression of free radical load and reduction in neutrophil activation and infiltration. Rheumatol Int 33(3):657–663. https://doi.org/10.1007/s00296-012-2430-4 CrossRefGoogle Scholar
- 6.Kodydková J, Vávrová L, Kocík M, Žák A (2014) Human catalase, its polymorphisms, regulation and changes of its activity in different diseases. Folia Biol (Praha) 60(4):153–167Google Scholar
- 9.Sklodowska M, Gromadzinska J, Biernacka M, Wasowicz W, Wolkanin P, Marszalek A et al (1996) Vitamin E, thiobarbituric acid reactive substance concentrations and superoxide dismutase activity in the blood of children with juvenile rheumatoid arthritis. Clin Exp Rheumatol 14(4):433–439Google Scholar
- 10.Ensembl base (2018) Transcript: CAT-201. http://www.ensembl.org/Homo_sapiens/Transcript/Summary?db=core;g=ENSG00000121691;r=11:34438925-34472062;t=ENST00000241052. Accessed 22 Oct 2018
- 13.Quick SK, Shields PG, Nie J, Platek ME, McCann SE, Hutson AD et al (2008) Effect modification by catalase genotype suggests a role for oxidative stress in the association of hormone replacement therapy with postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev 17(5):1082–1087. https://doi.org/10.1158/1055-9965.EPI-07-2755 CrossRefGoogle Scholar
- 17.Horneff G, Schulz AC, Klotsche J, Hospach A, Minden K, Foeldvari I et al (2017) Experience with etanercept, tocilizumab and interleukin-1 inhibitors in systemic onset juvenile idiopathic arthritis patients from the BIKER registry. Arthritis Res Ther 19(1):256. https://doi.org/10.1186/s13075-017-1462-2 CrossRefGoogle Scholar
- 19.Forsberg L, Lyrenas L, de Faire U, Morgenstern R (2001) A common functional C-T substitution polymorphism in the promoter region of the human catalase gene influences transcription factor binding, reporter gene transcription and is correlated to blood catalase levels. Free Radic Biol Med 30(5):500–505CrossRefGoogle Scholar
- 21.Goţia S, Popovici I, Hermeziu B (2001) Antioxidant enzymes levels in children with juvenile rheumatoid arthritis. Rev Med Chir Soc Med Nat Iasi 105(3):499–503Google Scholar
- 24.Winsz-Szczotka K, Komosińska-Vassev K, Kuźnik-Trocha K, Gruenpeter A, Lachór-Motyka I, Olczyk K (2014) Influence of proteolytic–antiproteolytic enzymes and prooxidative–antioxidative factors on proteoglycan alterations in children with juvenile idiopathic arthritis. Clin Biochem 47(9):829–834. https://doi.org/10.1016/j.clinbiochem.2014.01.027 CrossRefGoogle Scholar
- 28.Alexeeva EI, Namazova-Baranova LS, Bzarova TM, Valieva SI, Denisova RV, Sleptsova TV et al (2017) Predictors of the response to etanercept in patients with juvenile idiopathic arthritis without systemic manifestations within 12 months: results of an open-label, prospective study conducted at the National Scientific and Practical Center of Children’s Health, Russia. Pediatr Rheumatol Online J 15(1):51. https://doi.org/10.1186/s12969-017-0178-9 CrossRefGoogle Scholar
- 32.Alexeeva E, Dvoryakovskaya T, Denisova R, Sleptsova T, Isaeva K, Chomahidze A, Fetisova A, Mamutova A, Alshevskaya A, Gladkikh V, Moskalev A (2018) Comparative analysis of the etanercept efficacy in children with juvenile idiopathic arthritis under the age of 4 years and children of older age groups using the propensity score matching method. Mod Rheumatol. https://doi.org/10.1080/14397595.2018.1516329 Google Scholar
- 33.Basic J, Pavlovic D, Jevtovic-Stoimenov T, Vojinovic J, Susic G, Stojanovic I et al (2010) Etanercept reduces matrix metalloproteinase-9 level in children with polyarticular juvenile idiopathic arthritis and TNF-α-308GG genotype. J Physiol Biochem 66(2):173–180. https://doi.org/10.1007/s13105-010-0022-x CrossRefGoogle Scholar
- 35.Constantin T, Foeldvari I, Vojinovic J, Horneff G, Burgos-Vargas R, Nikishina I et al (2016) Two-year efficacy and safety of etanercept in pediatric patients with extended oligoarthritis, enthesitis-related arthritis, or psoriatic arthritis. J Rheumatol 43(4):816–824. https://doi.org/10.3899/jrheum.150430 CrossRefGoogle Scholar