Associations between paraoxonase 1 (PON1) polymorphisms and susceptibility and PON1 activity in rheumatoid arthritis patients, and comparison of PON1 activity in patients and controls: a meta-analysis

  • Sang-Cheol Bae
  • Young Ho LeeEmail author
Original Article



We reviewed the associations between paraoxonase 1 (PON1) polymorphisms and susceptibility and PON1 activity in rheumatoid arthritis (RA) patients and compared PON1 activity between RA patients and controls.


We conducted a meta-analysis of PON1 Q192R and L55M polymorphism and RA risk data and determined the associations between PON1 Q192R polymorphism and PON1 activity in RA patients. We also compared serum/plasma PON1 activity levels in RA patients and controls.


Twelve studies were included in this meta-analysis. No association was observed between RA and the PON1 192R allele in any study subject (OR = 0.967, 95% CI = 0.829–1.129, p = 0.674). Analysis using recessive, dominant, or homozygous contrast models revealed no association between the PON1 192R allele and RA. Meta-analysis showed no association between RA and the PON1 55M allele (OR = 1.400, 95% CI = 0.738–2.658, p = 0.308). In the meta-analysis, PON1 activity was significantly higher in the RR genotype than in the QQ (SMD = 2.975, 95% CI = 2.157–3.792, p < 0.001) and QR (SMD = 1.265, 95% CI = 0.898–1.633, p < 0.001) genotypes. PON1 activity was significantly lower in the RA group than in the control group (SMD = − 3.176, 95% CI = − 5.070 to − 1.283, p < 0.001).


We found no association between the PON1 Q192R and L55M polymorphisms and susceptibility to RA, while PON1 Q192R polymorphism was associated with PON1 activity in RA patients; we found significantly lower PON1 activity in RA patients.

Key points

PON1 Q192R polymorphism is associated with PON1 activity in RA patients..

PON1 activity is significantly lower in RA patients..


Activity Polymorphism PON1 Rheumatoid arthritis 


Funding information

This study was supported in part by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) and funded by the Ministry of Science & ICT (NRF-2017M3A9B4050335), Republic of Korea.

Compliance with ethical standards




  1. 1.
    Harris ED Jr (1990) Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med 322:1277–1289CrossRefGoogle Scholar
  2. 2.
    Choi SJ, Rho YH, Ji JD, Song GG, Lee YH (2006) Genome scan meta-analysis of rheumatoid arthritis. Rheumatology (Oxford) 45:166–170CrossRefGoogle Scholar
  3. 3.
    Karlson EW, Lee IM, Cook NR, Manson JE, Buring JE, Hennekens CH (1999) A retrospective cohort study of cigarette smoking and risk of rheumatoid arthritis in female health professionals. Arthritis Rheum 42:910–917CrossRefGoogle Scholar
  4. 4.
    Halliwell B (1994) Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet 344:721–724CrossRefGoogle Scholar
  5. 5.
    Pattison DJ, Winyard PG (2008) Dietary antioxidants in inflammatory arthritis: do they have any role in etiology or therapy? Nat Clin Pract Rheumatol 4:590–596CrossRefGoogle Scholar
  6. 6.
    Furlong CE, Richter RJ, Seidel SL, Costa LG, Motulsky AG (1989) Spectrophotometric assays for the enzymatic hydrolysis of the active metabolites of chlorpyrifos and parathion by plasma paraoxonase/arylesterase. Anal Biochem 180:242–247CrossRefGoogle Scholar
  7. 7.
    Hillier LW, Fulton RS, Fulton LA et al (2003) The DNA sequence of human chromosome 7. Nature 424:157–164CrossRefGoogle Scholar
  8. 8.
    Scacchi R, Corbo RM, Rickards O, De Stefano GF (2003) New data on the world distribution of paraoxonase (PON1 Gln 192 --> Arg) gene frequencies. Hum Biol 75:365–373CrossRefGoogle Scholar
  9. 9.
    Davies HG, Richter RJ, Keifer M, Broomfield CA, Sowalla J, Furlong CE (1996) The effect of the human serum paraoxonase polymorphism is reversed with diazoxon, soman and sarin. Nat Genet 14:334–336CrossRefGoogle Scholar
  10. 10.
    Tanhapour M, Shahmohamadnejad S, Vaisi-Raygani A, Kiani A, Shakiba Y, Rahimi Z, Bahrehmand F, Shakiba E, Vaisi-Raygani AA, Alibakhshi R, Eivazi A, Pourmotabbed T (2018) Association between activity and genotypes of paraoxonase1 L55M (rs854560) increases the disease activity of rheumatoid arthritis through oxidative stress. Mol Biol Rep.
  11. 11.
    Rodriguez-Carrio J, Lopez-Mejias R, Alperi-Lopez M, Lopez P, Ballina-Garcia FJ, Gonzalez-Gay MA, Suarez A (2016) Paraoxonase 1 activity is modulated by the rs662 polymorphism and IgG anti-high-density lipoprotein antibodies in patients with rheumatoid arthritis: potential implications for cardiovascular disease. Arthritis Rheumatol 68:1367–1376CrossRefGoogle Scholar
  12. 12.
    Shahmohamadnejad S, Vaisi-Raygani A, Shakiba Y, Kiani A, Rahimi Z, Bahrehmand F, Shakiba E, Pourmotabbed T (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 48:63–69CrossRefGoogle Scholar
  13. 13.
    El-Banna H, Jiman-Fatani A (2014) Anti-cyclic citrullinated peptide antibodies and paraoxonase-1 polymorphism in rheumatoid arthritis. BMC Musculoskelet Disord 15:379CrossRefGoogle Scholar
  14. 14.
    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 65:2765–2772CrossRefGoogle Scholar
  15. 15.
    Hashemi M, Moazeni-Roodi AK, Fazaeli A, Sandoughi M, Taheri M, Bardestani GR, Zakeri Z, Kordi-Tamandani DM, Ghavami S (2010) The L55M polymorphism of paraoxonase-1 is a risk factor for rheumatoid arthritis. Genet Mol Res 9:1735–1741CrossRefGoogle Scholar
  16. 16.
    Hashemi M, Moazeni-Roodi AK, Fazaeli A, Sandoughi M, Bardestani GR, Kordi-Tamandani DM, Ghavami S (2010) Lack of association between paraoxonase-1 Q192R polymorphism and rheumatoid arthritis in Southeast Iran. Genet Mol Res 9:333–339CrossRefGoogle Scholar
  17. 17.
    Bindal UD, Saxena R, Siddiqui MH, Sharma D (2016) Correlation of Paraoxonase status with disease activity score and systemic inflammation in rheumatoid arthritic patients. J Clin Diagn Res 10:BC01–BC05Google Scholar
  18. 18.
    Rodriguez-Carrio J, Alperi-Lopez M, Lopez-Mejias R, Lopez P, Ballina-Garcia FJ, Abal F, Gonzalez-Gay MA, Suarez A (2016) Antibodies to paraoxonase 1 are associated with oxidant status and endothelial activation in rheumatoid arthritis. Clin Sci (Lond) 130:1889–1899CrossRefGoogle Scholar
  19. 19.
    Tanimoto N, Kumon Y, Suehiro T, Ohkubo S, Ikeda Y, Nishiya K, Hashimoto K (2003) Serum paraoxonase activity decreases in rheumatoid arthritis. Life Sci 72:2877–2885CrossRefGoogle Scholar
  20. 20.
    Isik A, Koca SS, Ustundag B, Celik H, Yildirim A (2007) Paraoxonase and arylesterase levels in rheumatoid arthritis. Clin Rheumatol 26:342–348CrossRefGoogle Scholar
  21. 21.
    Baskol G, Demir H, Baskol M, Kilic E, Ates F, Kocer D, Muhtaroglu S (2005) Assessment of paraoxonase 1 activity and malondialdehyde levels in patients with rheumatoid arthritis. Clin Biochem 38:951–955CrossRefGoogle Scholar
  22. 22.
    Lee YH (2018) Association between the neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio and rheumatoid arthritis and their correlations with the disease activity: a meta-analysis. J Rheum Dis 25:169–178CrossRefGoogle Scholar
  23. 23.
    Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097CrossRefGoogle Scholar
  24. 24.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558CrossRefGoogle Scholar
  25. 25.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188CrossRefGoogle Scholar
  26. 26.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634CrossRefGoogle Scholar
  27. 27.
    Khoja SO, Miedany YE, Iyer AP, Bahlas SM, Balamash KS, Elshal MF (2017) Association of paraoxonase 1 polymorphism and serum 25-hydroxyvitamin D with the risk of cardiovascular disease in patients with rheumatoid arthritis. Clin Lab 63:1841–1849CrossRefGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  1. 1.Department of RheumatologyHanyang University Hospital for Rheumatic DiseasesSeoulSouth Korea
  2. 2.Department of Rheumatology, Korea University Anam HospitalKorea University College of MedicineSeoulSouth Korea

Personalised recommendations