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Association between activity and genotypes of paraoxonase1 L55M (rs854560) increases the disease activity of rheumatoid arthritis through oxidative stress

  • Maryam Tanhapour
  • Shiva Shahmohamadnejad
  • Asad Vaisi-Raygani
  • Amir Kiani
  • Yadola Shakiba
  • Zohreh Rahimi
  • Fariborz Bahrehmand
  • Ebrahim Shakiba
  • Ali-Akbar Vaisi-Raygani
  • Reza Alibakhshi
  • Atefeh Eivazi
  • Tayebeh Pourmotabbed
Original Article
  • 15 Downloads

Abstract

Rheumatoid arthritis (RA) is considered as a long-term autoimmune disorder. Gene polymorphism and oxidative stress might be involved in the pathogenesis of the disease. We aimed to determine the association between PON-1L55M polymorphism and its effects on inflammatory markers such as anti-cytroline circulated-peptide (CCP)-antibodies, C-reactive protein (CRP), neopterin serum concentration, arylesterase (ARE) and butyrylcholinesterase (BuChE) activities and total-antioxidant-capacity (TAC) level with the activity of disease in RA patients. This case-control study consisted of 419 RA patients and 397 gender–age-matched unrelated healthy controls from the west of Iran. PON1-L55M polymorphism was detected by real-time-PCR. The TAC level, serum BuChE and ARE activities were determined spectrophotometrically. Anti-CCP-antibody and CRP were measured by ELISA and neopterin level was detected by HPLC. The PON1-M55 allele was associated with increased risk of the RA in cases with moderate or high activity (OR = 1.43, p = 0.023) and also in cases with the presence of anti-CCP antibody (OR = 1.51, p = 0.009). Synergistic effects of PON1 M55 and Q192 alleles resulted in 2.14 times (p = 0.021) increased disease activity among RA patients with moderate or high activity of the disease. RA patients carried both M (PON1 L55M) and Q alleles (PON1Q192R) had higher concentrations of neopterin (p = 0.003), anti-CCP-antibody (p < 0.001) and CRP (p = 0.026) and significantly lower TAC level (p < 0.001) and ARE (p < 0.001) activity compared to controls. The current study suggests there might be a relationship between genetic and activity of PON. Also, the PON1L55M and PON1Q192R could act in synergy to increase the risk of RA and enhance the level of oxidative stress markers.

Keywords

Paraoxonase genotypes (PON) Rheumatoid arthritis (RA) Anti-CCP-antibody (anti-cytroline circulated peptide (CCP)-antibodies) CRP (C-reactive protein) Neopterin Butyrylcholinesterase activity (BuChE) Arylesterase activity (ARE) 

Abbreviations

RA

Rheumatoid arthritis

MDA

Malondialdehyde

ROS

Reactive oxygen species

CAD

Coronary artery disease

CCP-antibodies

Anti-CCP-antibody anti-cytroline circulated peptide

CRP

C-reactive protein

BuChE

Butyrylcholinesterase activity

ARE

Arylesterase activity

PON

Paraoxonase

Notes

Acknowledgements

This work was performed in partial fulfillment of requirements for a M.Sc by degree in Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran (Shiva Shahmohamadnejad). All authors contributed equally to this study.

Funding

This study was funded by Kermanshah University of Medical Sciences, Kermanshah, Iran, Grant No. 90324.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Mellado M, Martinez-Munoz L, Cascio G, Lucas P, Pablos JL, Rodriguez-Frade JM (2015) T cell migration in rheumatoid arthritis. Front Immunol 6:384CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Mateen S, Moin S, Khan AQ, Zafar A, Fatima N (2016) Increased reactive oxygen species formation and oxidative stress in rheumatoid arthritis. PLoS ONE 11(4):e0152925CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Alamanos Y, Voulgari PV, Drosos AA (2006) Incidence and prevalence of rheumatoid arthritis, based on the 1987 American College of Rheumatology criteria: a systematic review. Semin Arthritis Rheum 36(3):182–188CrossRefPubMedGoogle Scholar
  4. 4.
    Y.Yazici SA, Paget (2000) Elderly-onset rheumatoid arthritis. Rheum Dis Clin N Am 26(3):517–526CrossRefGoogle Scholar
  5. 5.
    Anderson KO, Bradley LA, Young LD, McDaniel LK, Wise CM (1985) Rheumatoid arthritis: review of psychological factors related to etiology, effects, and treatment. Psychol bull 98(2):358CrossRefPubMedGoogle Scholar
  6. 6.
    Tak PP, Zvaifler NJ, Green DR, Firestein GS (2000) Rheumatoid arthritis and p53: how oxidative stress might alter the course of inflammatory diseases. Immunol Today 21(2):78–82CrossRefPubMedGoogle Scholar
  7. 7.
    Vaisi-Raygani A, Ghaneialvar H, Rahimi Z, Tavilani H, Pourmotabbed T, Shakiba E, Vaisi-Raygani A, Kiani A, Aminian M, Alibakhshi R, Bartels C (2011) Paraoxonase Arg 192 allele is an independent risk factor for three-vessel stenosis of coronary artery disease. Mol Biol Rep 38(8):5421–5428 C.CrossRefPubMedGoogle Scholar
  8. 8.
    Charles-Schoeman C, Lee YY, Shahbazian A, Gorn AH, Fitzgerald J, Ranganath VK, Taylor M, Ragavendra N, McMahon M, Elashoff D, Reddy ST (2013) Association of paraoxonase 1 gene polymorphism and enzyme activity with carotid plaque in rheumatoid arthritis. Arthritis Rheum 65(11): 2765–2772CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Charles-Schoeman C, Meriwether D, Lee YY, Shahbazian A, Reddy ST (2018) High levels of oxidized fatty acids in HDL are associated with impaired HDL function in patients with active rheumatoid arthritis. Clin Rheumatol 37(3):615–622CrossRefPubMedGoogle Scholar
  10. 10.
    Bahrehmand F, Vaisi-Raygani A, Ahmadi R, Kiani A, Rahimi Z, Tavilani H et al (2013) Paraoxonase (PON1) 55 polymorphism and association with systemic lupus erythematosus. Iran J Allergy Asthma Immunol 12(3):211–219PubMedGoogle Scholar
  11. 11.
    Shahmohamadnejad S, Vaisi-Raygani A, Shakiba Y, Kiani A, Rahimi Z, Bahrehmand F et al (2015) Association between butyrylcholinesterase activity and phenotypes, paraoxonase192 rs662 gene polymorphism and their enzymatic activity with severity of rheumatoid arthritis: correlation with systemic inflammatory markers and oxidative stress, preliminary report. Clin Biochem 48:63–69CrossRefPubMedGoogle Scholar
  12. 12.
    Bahrehmand F, Vaisi-Raygani A, Rahimi Z, Ahmadi R, Kiani A, Tavilani H et al (2014) Synergistic effects of BuChE non-UU phenotype and paraoxonase (PON1) 55 M allele on the risk of systemic lupus erythematosus: influence on lipid and lipoprotein metabolism and oxidative stress, preliminary report. Lupus 23(3):263–272CrossRefPubMedGoogle Scholar
  13. 13.
    Vaisi-Raygani A, Tavilani H, Zahrai M, Rahimi Z, Sheikh N, Aminian M et al (2009) Serum butyrylcholinesterase activity and phenotype associations with lipid profile in stroke patients. Clin Biochem 42(3):210–214CrossRefPubMedGoogle Scholar
  14. 14.
    Rahimi Z, Ahmadi R, Vaisi-Raygani A, Rahimi Z, Bahrehmand F, Parsian A (2013) Butyrylcholinesterase (BChE) activity is associated with the risk of preeclampsia: influence on lipid and lipoprotein metabolism and oxidative stress. J Matern Fetal Neonatal Med 26(16):1590–1594CrossRefPubMedGoogle Scholar
  15. 15.
    Asefi M, Vaisi-Raygani A, Bahrehmand F, Kiani A, Rahimi Z, Nomani H et al (2012) Paraoxonase 1 (PON1) 55 polymorphism, lipid profiles and psoriasis. Br J Dermatol 167(6):1279–1286CrossRefPubMedGoogle Scholar
  16. 16.
    van Venrooij WJ, van Beers JJ, Pruijn GJ (2011) Anti-CCP antibodies: the past, the present and the future. Nat Rev Rheumatol 7(7):391–398CrossRefPubMedGoogle Scholar
  17. 17.
    Arshadi D, Nikbin B, Shakiba Y, Kiani A, Jamshidi AR, Boroushaki MT (2013) Plasma level of neopterin as a marker of disease activity in treated rheumatoid arthritis patients: association with gender, disease activity andd anti-CCP antibod. Int Immunopharmacol 17(3):763–767CrossRefPubMedGoogle Scholar
  18. 18.
    González-Gay MA, González-Juanatey C (2014) Inflammation and lipid profile in rheumatoid arthritis: bridging an apparent paradox. Ann Rheum Dis 73(7):1281–1283CrossRefGoogle Scholar
  19. 19.
    von Versen-Hoeynck FM, Hubel CA, Gallaher MJ, Gammill HS, Powers RW (2009) Plasma levels of inflammatory markers neopterin, sialic acid, and C-reactive protein in pregnancy and preeclampsia. Am J hypertens 22(6):687–692CrossRefGoogle Scholar
  20. 20.
    Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324CrossRefPubMedGoogle Scholar
  21. 21.
    Humbert R, Adler DA, Disteche CM, Hassett C, Omiecinski CJ, Furlong CE (1993) The molecular basis of the human serum paraoxonase activity polymorphism. Nat Genet 3(1):73–76CrossRefPubMedGoogle Scholar
  22. 22.
    Vaisi-Raygani A, Rahimi Z, Entezami H, Kharrazi H, Bahrhemand F, Tavilani H et al (2008) Butyrylcholinesterase K variants increase the risk of coronary artery disease in the population of western Iran, Scand. J Clin Lab Invest 68(2):123–129CrossRefGoogle Scholar
  23. 23.
    Teranishi M, Uchida Y, Nishio N, Kato K, Otake H, Yoshida T et al (2012) Polymorphisms in genes involved in oxidative stress response in patients with sudden sensorineural hearing loss and Meniere’s disease in a Japanese population. DNA Cell Biol 31(10):1555–1562CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Sokka T (2003) Work disability in early rheumatoid arthritis. Clin Exp Rheumatol 21(5 Suppl 31):S71–S74PubMedGoogle Scholar
  25. 25.
    Hirvonen H, Kautiainen H, Moilanen E, Mikkelsson M, Leirisalo-Repo M (2017) The effect of cryotherapy on total antioxidative capacity in patients with active seropositive rheumatoid arthritis. Rheumatol Int 37(9):1481–1487CrossRefPubMedGoogle Scholar
  26. 26.
    Tanhapour M, Vaisi-Raygani A, Bahrehmand F, Khazaei M, Kiani A, Rahimi Z et al (2016) Association between the cytotoxic T-lymphocyte antigen-4 mutations and the susceptibility to systemic lupus erythematosus; contribution markers of inflammation and oxidative stress. Cell Mol Biol 62(12):56–61PubMedGoogle Scholar
  27. 27.
    Tanhapour M, Miri A, Vaisi-Raygani A, Bahrehmand F, Kiani A, Rahimi Z et al (2017) Synergism between apolipoprotein E Ɛ4 allele and paraoxonase (PON1) 55-M allele is associated with risk of systemic lupus erythematosus. Clin Rheumatol 37(4):971–977CrossRefPubMedGoogle Scholar
  28. 28.
    Chen H, Ding S, Zhou M, Wu X, Liu X, Liu J et al (2017) PON1 L55M and Q192R gene polymorphisms and CAD risks in patients with hyperlipidemia: clinical study of possible associations, Herz 43(7):642–648CrossRefPubMedGoogle Scholar
  29. 29.
    Hashemi M, Moazeni-Roodi AK, Fazaeli A, Sandoughi M, Taheri M, Bardestani GR et al (2010) The L55M polymorphism of paraoxonase-1 is a risk factor for rheumatoid arthritis. Genet Mol Res 9(3):1735–1741CrossRefPubMedGoogle Scholar
  30. 30.
    Ates I, Yilmaz FM, Altay M, Yilmaz N, Berker D, Guler S (2015) The relationship between oxidative stress and autoimmunity in Hashimoto’s thyroiditis. Eur J Endocrinol 173(6):791–799CrossRefPubMedGoogle Scholar
  31. 31.
    Strickland FM, Li Y, Johnson K, Sun Z, Richardson BC (2015) CD4 (+) T cells epigenetically modified by oxidative stress cause lupus-like autoimmunity in mice. J Autoimmun 62:75–80CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Shah D, Mahajan N, Sah S, Nath SK, Paudyal B (2014) Oxidative stress and its biomarkers in systemic lupus erythematosus. J Biomed Sci 21:23CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Lo Gullo A, Mandraffino G, Sardo MA, D’Ascola A, Mamone F, Loddo S et al (2014) Circulating progenitor cells in rheumatoid arthritis: association with inflammation and oxidative stress. Scand J Rheumatol 43(3):184–193CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Maryam Tanhapour
    • 1
  • Shiva Shahmohamadnejad
    • 1
  • Asad Vaisi-Raygani
    • 1
  • Amir Kiani
    • 2
  • Yadola Shakiba
    • 3
  • Zohreh Rahimi
    • 4
  • Fariborz Bahrehmand
    • 4
  • Ebrahim Shakiba
    • 1
  • Ali-Akbar Vaisi-Raygani
    • 5
  • Reza Alibakhshi
    • 1
  • Atefeh Eivazi
    • 1
  • Tayebeh Pourmotabbed
    • 6
  1. 1.Fertility and Infertility Research CenterKermanshah University of Medical SciencesKermanshahIran
  2. 2.Pharmacceutical Sciences Research Center, School of PharmacyKermanshah University of Medical SciencesKermanshahIran
  3. 3.Regenerative Medicine Research CenterKermanshah University of Medical SciencesKermanshahIran
  4. 4.Medical Biology Research CenterKermanshah University of Medical SciencesKermanshahIran
  5. 5.Department of NursingKermanshah University of Medical SciencesKermanshahIran
  6. 6.Department of Microbiology, Immunology and BiochemistryUniversity of Tennessee, Health Science CenterMemphisUSA

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