Skip to main content
Log in

Influence of interleukin 17 A and 17 F polymorphisms in keratoconus

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

Until a few years ago, keratoconus was defined as a noninflammatory degenerative disease. However, recent studies have shown that the altered balance between inflammatory cytokines, proteases, and protease inhibitors, as well as free radicals and oxidants, have a crucial role in the pathogenesis of this disease. The aim of this study is to investigate whether interleukin 17 A G197A (rs2275913) and interleukin 17 F T7488C (rs763780) polymorphisms are associated with keratoconus in patients from a population of the northwestern region of the State of São Paulo, Brazil.

Methods and Results

35 patients and 61 controls were enrolled. Genotyping of interleukin 17 A G197A and interleukin 17 F T7488C polymorphisms was carried out using the polymerase chain reaction-restriction fragment length polymorphism technique. Statistical analyses were conducted using the chi-square test, and an odds ratio with a 95% confidence interval was also calculated to evaluate the association between polymorphisms and disease. Evaluating interleukin 17 F T7488C, we found that the TT genotype is associated as a risk factor for keratoconus (P = 0.04; OR = 3.01; CI 1.11–8.14). As for evaluating interleukin 17 A G197A, the allele and genotype frequencies between patients and controls were compared and no statistically significant differences were found.

Conclusions

Our data showed that the interleukin 17 F T7488C polymorphisms may exert an influence in keratoconus.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Availability of data and material

The authors confirm that the data supporting the findings of this study are available within the article.

Code availability

Not applicable.

References

  1. Hashemi H, Heydarian S, Hooshmand E et al (2020) The prevalence and risk factors for keratoconus: a systematic review and meta-analysis. Cornea 39:263–270. https://doi.org/10.1097/ICO.0000000000002150

    Article  PubMed  Google Scholar 

  2. Mounir A, El Saman IS, Anbar M (2019) The correlation between corneal topographic indices and corneal high order aberrations in keratoconus. Med hypothesis. Discov Innov Ophthalmol J 8:1–6

    Google Scholar 

  3. Michael A, Hauser JW (2012) The genetics of keratoconus: a review. Reprod Syst Sex Disord. https://doi.org/10.4172/2161-038x.s6-001

    Article  Google Scholar 

  4. Naderan M, Rajabi MT, Zarrinbakhsh P et al (2016) Association between family history and keratoconus severity. Curr Eye Res 41:1414–1418. https://doi.org/10.3109/02713683.2015.1128553

    Article  PubMed  Google Scholar 

  5. Ghassembaglou N, Djalilian AR (2016) Keratoconus; a true corneal disease. J Ophthalmic Vis Res 11:1–2

    Article  PubMed  PubMed Central  Google Scholar 

  6. Volatier TLA, Figueiredo FC, Connon CJ (2020) Keratoconus at a molecular level: a review. Anat Rec 303:1680–1688. https://doi.org/10.1002/ar.24090

    Article  CAS  Google Scholar 

  7. Barrientez B, Nicholas SE, Whelchel A et al (2019) Corneal injury: clinical and molecular aspects. Exp Eye Res 186:107709. https://doi.org/10.1016/j.exer.2019.107709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kapitanović Vidak H, Catela Ivković T, Jokić M et al (2012) The association between proinflammatory cytokine polymorphisms and cerebral palsy in very preterm infants. Cytokine 58:57–64. https://doi.org/10.1016/j.cyto.2011.12.018

    Article  CAS  PubMed  Google Scholar 

  9. Liu B, Li A, Wang H et al (2020) Exploring the key genes and pathways in the formation of corneal scar using bioinformatics analysis. Biomed Res Int 2020:1–10. https://doi.org/10.1155/2020/6247489

    Article  CAS  Google Scholar 

  10. Jun AS, Cope L, Speck C et al (2011) Subnormal cytokine profile in the tear fluid of keratoconus patients. PLoS ONE. https://doi.org/10.1371/journal.pone.0016437

    Article  PubMed  PubMed Central  Google Scholar 

  11. Cox ED, Hoffmann SC, DiMercurio BS et al (2001) Cytokine polymorphic analyses indicate ethnic differences in the allelic distribution of interleukin-2 and interleukin-6. Transplantation 72:720–726. https://doi.org/10.1097/00007890-200108270-00027

    Article  CAS  PubMed  Google Scholar 

  12. Wisse RPL, Kuiper JJW, Gans R et al (2015) Cytokine expression in keratoconus and its corneal microenvironment: a systematic review. Ocul Surf 13:272–283

    Article  PubMed  Google Scholar 

  13. Marcon CF, Ferreira PTM, Franco PS et al (2020) Macrophage migration inhibitory factor (MIF) and pregnancy may impact the balance of intestinal cytokines and the development of intestinal pathology caused by Toxoplasma gondii infection. Cytokine X 2:100034. https://doi.org/10.1016/j.cytox.2020.100034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Murugaiyan G, Saha B (2009) Protumor vs antitumor functions of IL-17. J Immunol 183:4169–4175. https://doi.org/10.4049/jimmunol.0901017

    Article  CAS  PubMed  Google Scholar 

  15. Da Cunha AP, Zhang Q, Prentiss M et al (2018) The hierarchy of proinflammatory cytokines in ocular inflammation. Curr Eye Res 43:553–565. https://doi.org/10.1080/02713683.2017.1410180

    Article  CAS  PubMed  Google Scholar 

  16. Reis PG, Ayo CM, Mattos LC, De, et al (2017) Genetic polymorphisms of IL17 and Chagas disease in the south and southeast of Brazil. J Immunol Res. https://doi.org/10.1155/2017/1017621

    Article  PubMed  PubMed Central  Google Scholar 

  17. Karolak JA, Gambin T, Pitarque JA et al (2017) Variants in SKP1, PROB1, and IL17B genes at keratoconus 5q31.1-q35.3 susceptibility locus identified by whole-exome sequencing. Eur J Hum Genet 25:73–78. https://doi.org/10.1038/ejhg.2016.130

    Article  CAS  PubMed  Google Scholar 

  18. Zacarias JMV, Sippert E, Tsuneto PY et al (2015) The influence of interleukin 17A and IL17F polymorphisms on chronic periodontitis disease in Brazilian patients. Mediators Inflamm. https://doi.org/10.1155/2015/147056

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ferrari G, Rama P (2020) The keratoconus enigma: a review with emphasis on pathogenesis. Ocul Surf 18:363–373. https://doi.org/10.1016/j.jtos.2020.03.006

    Article  PubMed  Google Scholar 

  20. Blackburn BJ, Jenkins MW, Rollins AM, Dupps WJ (2019) A review of structural and biomechanical changes in the cornea in aging, disease, and photochemical crosslinking. Front Bioeng Biotechnol 7:66. https://doi.org/10.3389/fbioe.2019.00066

    Article  PubMed  PubMed Central  Google Scholar 

  21. di Martino E, Ali M, Inglehearn CF (2019) Matrix metalloproteinases in keratoconus: too much of a good thing? Exp Eye Res 182:137–143. https://doi.org/10.1016/j.exer.2019.03.016

    Article  CAS  PubMed  Google Scholar 

  22. Gomes R, Do Nascimento EF, De Araújo FC (2007) Por que os homens buscam menos os serviços de saúde do que as mulheres? As explicações de homens com baixa escolaridade e homens com ensino superior. Cad Saude Publica 23:565–574. https://doi.org/10.1590/S0102-311X2007000300015

    Article  PubMed  Google Scholar 

  23. Martins ERC, Medeiros A, da S, Oliveira KL de et al (2020) Vulnerabilidade de homens jovens e suas necessidades de saúde. Esc Anna Nery 24:2020. https://doi.org/10.1590/2177-9465-ean-2019-0203

    Article  Google Scholar 

  24. Vieira UA, Araujo MDO, Araujo BDO, Paixão GPDN (2020) Percepção dos enfermeiros sore a (não) procura dos homens por Atenção Primária à Saúde. Rev Saúde Coletiva da UEFS 10:58. https://doi.org/10.13102/rscdauefs.v10i1.5454

    Article  Google Scholar 

  25. Chang SH, Dong C (2007) A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses. Cell Res 17:435–440. https://doi.org/10.1038/cr.2007.35

    Article  CAS  PubMed  Google Scholar 

  26. Turner DM, Williams DM, Sankaran D et al (1997) An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 24:1–8. https://doi.org/10.1111/j.1365-2370.1997.tb00001.x

    Article  CAS  PubMed  Google Scholar 

  27. Wang Y, Wei W, Zhang C et al (2016) Association of interleukin-1 gene single nucleotide polymorphisms with keratoconus in Chinese Han Population. Curr Eye Res 41:630–635. https://doi.org/10.3109/02713683.2015.1045083

    Article  CAS  PubMed  Google Scholar 

  28. Livshits LAA, Drozhzhyna GII, Kucherenko AMM et al (2020) Role of IL6 -174 G/C, IL10 1082G/A and IL10 -592 C/A in the pathogenesis of keratoconus and development of recurrent erosion in Ukrainian patients with lattice corneal dystrophy. Oftalmol Zh 85:3–11. https://doi.org/10.31288/OFTALMOLZH20202311

    Article  Google Scholar 

  29. Gabriel ML, Braga FB, Cardoso MR et al (2016) The association between pro-and anti-inflammatory cytokine polymorphisms and periventricular leukomalacia in newborns with hypoxic-ischemic encephalopathy. J Inflamm Res 9:59–67. https://doi.org/10.2147/JIR.S103697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jukema JB, Hoenderboom BM, Van Benthem BHB et al (2021) Can previous associations of single nucleotide polymorphisms in the tlr2, nod1, cxcr5, and il10 genes in the susceptibility to and severity of chlamydia trachomatis infections be confirmed? Pathogens 10:1–16. https://doi.org/10.3390/pathogens10010048

    Article  CAS  Google Scholar 

  31. Pereira APL, Trugilo KP, Okuyama NCM et al (2020) IL-10 c-592C>A (rs1800872) polymorphism is associated withcervical cancer. J Cancer Res Clin Oncol 146:1971–1978. https://doi.org/10.1007/s00432-020-03256-0

    Article  CAS  PubMed  Google Scholar 

  32. Espinoza JL, Takami A, Nakata K et al (2011) A genetic variant in the IL-17 promoter is functionally associated with acute graft-versus-host disease after unrelated bone marrow transplantation. PLoS ONE. https://doi.org/10.1371/journal.pone.0026229

    Article  PubMed  PubMed Central  Google Scholar 

  33. Cho YA, Lee J, Oh JH et al (2018) Inflammatory dietary pattern, IL-17F genetic variant, and the risk of colorectal cancer. Nutrients 10:1–11. https://doi.org/10.3390/nu10060724

    Article  CAS  Google Scholar 

  34. Vrgoc G, Vrbanec J, Eftedal RK et al (2018) Interleukin-17 and Toll-like Receptor 10 genetic polymorphisms and susceptibility to large joint osteoarthritis. J Orthop Res 36:1684–1693. https://doi.org/10.1002/jor.23823

    Article  CAS  PubMed  Google Scholar 

  35. Gao S, Mao C, Cheng J et al (2020) Association of IL-17A-197G/A and IL-17F-7488T/C polymorphisms and osteoarthritis susceptibility: a meta-analysis. Int J Rheum Dis 23:37–46. https://doi.org/10.1111/1756-185X.13737

    Article  CAS  PubMed  Google Scholar 

  36. Kaur R, Rawat A, Kumar S et al (2018) Association of genetic polymorphism of interleukin-17A & interleukin-17F with susceptibility of psoriasis. Indian J Med Res 148:422–426. https://doi.org/10.4103/ijmr.IJMR_1859_16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kawaguchi M, Takahashi D, Hizawa N et al (2006) IL-17F sequence variant (His161Arg) is associated with protection against asthma and antagonizes wild-type IL-17F activity. J Allergy Clin Immunol 117:795–801. https://doi.org/10.1016/j.jaci.2005.12.1346

    Article  CAS  PubMed  Google Scholar 

  38. Chen Z, Tato CM, Muul L et al (2007) Distinct regulation of interleukin-17 in human T helper lymphocytes. Arthritis Rheum 56:2936–2946. https://doi.org/10.1002/art.22866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Belardelli F (1995) Role of interferons and other cytokines in the regulation of the immune response. APMIS 103:161–179

    Article  CAS  PubMed  Google Scholar 

  40. Ionescu C, Corbu CG, Tanase C et al (2016) Inflammatory biomarkers profile as microenvironmental expression in keratoconus. Dis Markers 2016:1243819. https://doi.org/10.1155/2016/1243819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Shetty R, DʼSouza S, Khamar P et al (2020) Biochemical markers and alterations in keratoconus. Asia-Pacific J Ophthalmol (Philadelphia Pa) 9:533–540. https://doi.org/10.1097/APO.0000000000000332

    Article  Google Scholar 

  42. Najmi H, Mobarki Y, Mania K et al (2019) The correlation between keratoconus and eye rubbing: a review. Int J Ophthalmol 12:1775–1781. https://doi.org/10.18240/ijo.2019.11.17

    Article  PubMed  PubMed Central  Google Scholar 

  43. Gabr MA, Jing L, Helbling AR et al (2011) Interleukin-17 synergizes with IFNIγ or TNFα to promote inflammatory mediator release and intercellular adhesion molecule-1 (ICAM-1) expression in human intervertebral disc cells. J Orthop Res 29:1–7. https://doi.org/10.1002/jor.21206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Berger T, Szentmáry N, Latta L et al (2021) NF-κB, iNOS, IL-6, and collagen 1 and 5 expression in healthy and keratoconus corneal fibroblasts after 0.1% riboflavin UV-A illumination. Graefe’s Arch Clin Exp Ophthalmol. https://doi.org/10.1007/s00417-020-05058-z

Download references

Acknowledgements

We thank all participants for their precious contribution to the study and Renato Babos da Purificação for an English revision. Jim Hesson copyedited the manuscript (https://www.academicenglishsolutions.com).

Funding

This study was supported by grants from Brazilian Ministry of Science, Technology and Innovation – CNPq (to IBG and to LSK); Brazilian Ministry of Education – CAPES PhD Scholarship (Coordination of Improvement of Higher Education Personnel, Brazil – to AGL and to CMA); and by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grant number: 2015/17226-7 to GCAJr; 2018/16622-4 to LSK; 2018/09448-8 to GMFJr). The opinions, assumptions, and conclusions or recommendations expressed in this material are the responsibility of the authors and do not necessarily reflect the views of FAPESP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Author information

Authors and Affiliations

Authors

Contributions

Conceived and designed the experiments: CCB, CMA, GCAJr, GMFJ, LC. Performed the experiments: IBG, AGL, LSK. Performed the enrollment of patients, sample collection, and developed the clinical evaluation and clinical analyses: GCAJr. Analyzed the data: IBG, CMA, LCM, CCB, LC. Wrote the paper: IBG, GCAJr, CMA, and CCB. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Cinara Cássia Brandão.

Ethics declarations

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical approval

This study was approved by the Research Ethics Committee of FAMERP (CAAE 44071315.7.0000.5415) and are in accordance with the Helsinki Declaration.

Consent to participate

An informed-consent form was signed by all participants who were adults, and by the parents/legally authorized representatives of the minors.

Consent for publication

All authors have contributed significantly and agree with publication the content of the paper.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gomes, I.B., Ayo, C.M., Lopes, A.G. et al. Influence of interleukin 17 A and 17 F polymorphisms in keratoconus. Mol Biol Rep 48, 7165–7170 (2021). https://doi.org/10.1007/s11033-021-06708-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-021-06708-z

Keywords

Navigation