Skip to main content
SpringerLink
Log in

Toll-like receptor 7 gene single nucleotide polymorphisms and the risk for systemic lupus erythematosus: a case-control study

Einzelnukleotidpolymorphismen im Toll-like-receptor-7-Gen (TLR7) und das Risiko eines systemischen Lupus erythematodes: eine Fall-Kontroll-Studie

  • Originalien
  • Published:
Zeitschrift für Rheumatologie Aims and scope Submit manuscript

Abstract

Background

Toll-like receptors (TLRs) are a family of pattern-recognition receptors which play a role in eliciting innate/adaptive immune responses and developing chronic inflammation. So, the aim of this study was to analyze the effect of TLR7 gene single nucleotide polymorphisms (SNPs) rs3853839 and rs179019 on systemic lupus erythematosus (SLE) susceptibility and to assess their relations with various clinical and laboratory data of the patients.

Methods

This is a case–control study including 50 SLE female patients and 50 healthy controls. TLR7 rs3853839 and rs179019 genotyping was performed using real-time polymerase chain reaction (PCR) TaqMan-based allelic discrimination assay.

Results

Regarding rs3853839, there was a statistically significant difference in the distribution of the genotypes between SLE patients and the control group in our study (P = 0.009). A significant association was detected between TLR7 genotypes (rs385389) and lupus nephritis (p = 0.021). Regarding rs179019, there was no statistically significant difference in the distribution of the genotypes between SLE patients and the control group in our study (P = 0.271)

Conclusion

This study revealed the plausible role of TLR7 rs3853839 SNP in SLE in Egyptian women.

Zusammenfassung

Hintergrund

„Toll-like receptors” (TLR) sind eine Familie von Mustererkennungsrezeptoren, die an der Auslösung von angeborenen oder adaptiven Immunreaktionen und an der Entwicklung einer chronischen Entzündung beteiligt sind. Ziel dieser Studie war es daher, die Wirkung der Einzelnukleotidpolymorphismen (SNP) rs3853839 und rs179019 in TLR7 auf die Anfälligkeit für einen systemischen Lupus erythematodes (SLE) zu untersuchen. Zudem sollte ihr Zusammenhang mit verschiedenen klinischen und laboranalytischen Patientendaten ermittelt werden.

Methoden

In die vorliegende Fall-Kontroll-Studie wurden 50 Patientinnen mit SLE und 50 gesunde Kontrollen eingeschlossen. Die Genotypisierung für TLR7 rs3853839 und rs179019 wurde mithilfe eines Real-time-Polymerase-Kettenreaktions-TaqMan-basierten Assays zur Alleldifferenzierung durchgeführt.

Ergebnisse

Für rs3853839 bestand in unserer Studie ein statistisch signifikanter Unterschied bezüglich der Genotypverteilung zwischen SLE-Patientinnen und der Kontrollgruppe (p = 0,009). Eine signifikante Assoziation wurde zwischen TLR7-Genotypen (rs385389) und Lupusnephritis gefunden (p = 0,021). Für rs179019 bestand in unserer Studie kein statistisch signifikanter Unterschied bezüglich der Genotypverteilung zwischen SLE-Patientinnen und der Kontrollgruppe (p = 0,271).

Schlussfolgerung

Diese Studie zeigt die plausible Bedeutung des TLR7-rs3853839-SNP für den SLE bei ägyptischen Frauen.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Celhar T, Fairhurst A‑M (2014) Toll-like receptors in systemic lupus erythematosus: potential for personalized treatment. Front Pharmacol 5:265

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783–801

    Article  PubMed  CAS  Google Scholar 

  3. Banchereau J, Pascual V (2006) Type I interferon in systemic lupus erythematosus and other autoimmune diseases. Immunity 25:383–392

    Article  PubMed  CAS  Google Scholar 

  4. Montero Vega MT, de Andres Martin A (2008) Toll-like receptors: a family of innate sensors of danger that alert and drive immunity. Allergol Immunopathol (Madr) 36(6):347–357

    Article  CAS  Google Scholar 

  5. Hurst J, von Landenberg P (2008) Toll-like receptors and autoimmunity. Autoimmun Rev 7(3):204–208

    Article  PubMed  CAS  Google Scholar 

  6. Lyn-Cook BD, Xie C, Oates J, Treadwell E, Word B, Hammons G, Wiley K (2014) Increased expression of Toll-like receptors (TLRs) 7 and 9 and other cytokines in systemic lupus erythematosus (SLE) patients: ethnic differences and potential new targets for therapeutic drugs. Mol Immunol 61:38–43

    Article  PubMed  CAS  Google Scholar 

  7. Enevold C, Nielsen CH, Jacobsen RS, Hermansen MLF, Molbo D, Avlund K, Bendtzen K, Jacobsen S (2014) Single nucleotide polymorphisms in genes encoding toll-like receptors 7, 8 and 9 in Danish patients with systemic lupus erythematosus. Mol Biol Rep 41:5755–5763

    Article  PubMed  CAS  Google Scholar 

  8. Savitsky D, Tamura T, Yanai H, Taniguchi T (2010) Regulation of immunity and oncogenesis by the IRF transcription factor family. Cancer Immunol Immunother 59(4):489–510

    Article  PubMed  CAS  Google Scholar 

  9. O’Neill LA, Sheedy FJ, Mccoy CE (2011) MicroRNAs: the fine-tuners of Toll-like receptor signaling. Nat Rev Immunol 11:163–175

    Article  PubMed  CAS  Google Scholar 

  10. Shen N, Fu Q, Deng Y, Qian X, Zhao J, Kaufman KM, Wu YL, Yu CY, Tang Y, Chen JY, Yang W, Wong M, Kawasaki A, Tsuchiya N, Sumida T, Kawaguchi Y, Howe HS, Mok MY, Bang SY, Liu FL, Chang DM, Takasaki Y, Hashimoto H, Harley JB, Guthridge JM, Grossman JM, Cantor RM, Song YW, Bae SC, Chen S, Hahn BH, Lau YL, Tsao BP (2010) Sex-specific association of X‑linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus. Proc Natl Acad Sci U S A 107:15838–15843

    Article  PubMed  PubMed Central  Google Scholar 

  11. Deng Y, Zhao J, Sakurai D, Kaufman KM, Edberg JC, Kimberly RP, Kamen DL, Gilkeson GS, Jacob CO, Scofield RH, Langefeld CD, Kelly JA, Ramsey-Goldman R, Petri MA, Reveille JD, Vilá LM, Alarcón GS, Vyse TJ, Pons-Estel BA, Argentine Collaborative Group, Freedman BI, Gaffney PM, Sivils KM, James JA, Gregersen PK, Anaya JM, Niewold TB, Merrill JT, Criswell LA, Stevens AM, Boackle SA, Cantor RM, Chen W, Grossman JM, Hahn BH, Harley JB, Alarcόn-Riquelme ME, BIOLUPUS and GENLES networks, Brown EE, Tsao BP (2011) MicroRNA-3148 modulates allelic expression of Toll-like receptor 7 variant associated with systemic lupus erythematosus. PLOS Genet 9(2):e1003336

    Article  CAS  Google Scholar 

  12. Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, Bruce IN, Isenberg D, Wallace DJ, Nived O, Sturfelt G, Ramsey-Goldman R, Bae SC, Hanly JG, Sánchez-Guerrero J, Clarke A, Aranow C, Manzi S, Urowitz M, Gladman D, Kalunian K, Costner M, Werth VP, Zoma A, Bernatsky S, Ruiz-Irastorza G, Khamashta MA, Jacobsen S, Buyon JP, Maddison P, Dooley MA, van Vollenhoven RF, Ginzler E, Stoll T, Peschken C, Jorizzo JL, Callen JP, Lim SS, Fessler BJ, Inanc M, Kamen DL, Rahman A, Steinsson K, Franks AG Jr, Sigler L, Hameed S, Fang H, Pham N, Brey R, Weisman MH, McGwin G Jr, Magder LS (2012) Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64:2677–2686

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640

    Article  PubMed  CAS  Google Scholar 

  14. Scofield RH, Bruner GR, Namjou B, Kimberly RP, Ramsey-Goldman R, Petri M, Reveille JD, Alarcón GS, Vilá LM, Reid J, Harris B, Li S, Kelly JA, Harley JB (2008) Klinefelter’s syndrome (47, XXY) in male systemic lupus erythematosus patients: support for the notion of a gene-dose effect from the X chromosome. Arthritis Rheum 58(8):2511–2517

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kawasaki A, Furukawa H, Kondo Y, Ito S, Hayashi T, Kusaoi M, Matsumoto I, Tohma S, Takasaki Y, Hashimoto H, Sumida T, Tsuchiya N (2011) TLR7 single-nucleotide polymorphisms in the 3′ untranslated region and intron 2 independently contribute to systemic lupus erythematosus in Japanese women: a case-control association study. Arthritis Res Ther 13:R41

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Laska MJ, Troldborg A, Hansen B, Stengaard-Pedersen K, Junker P, Nexø BA, Voss A (2014) Polymorphisms within Toll-like receptors are associated with systemic lupus erythematosus in a cohort of Danish females. Rheumatology 53(1):48–55

    Article  PubMed  CAS  Google Scholar 

  17. Horton CG, Pan Z‑J, Farris AD (2010) Targeting Toll-like receptors for treatment of SLE. Mediators Inflamm:9. doi:10.1155/2010/498980

Download references

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Clinical Pathology, Kasr Al Ainy Hospital, Cairo University, Cairo, Egypt

    I. I. Raafat, N. El Guindy, R. M. H. Shahin & L. A. Samy

  2. Department of Rheumatology and Rehabilitation, Kasr Al Ainy Hospital, Cairo University, Cairo, Egypt

    R. M. El Refai MD

Authors
  1. I. I. Raafat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. El Guindy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. M. H. Shahin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. A. Samy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. M. El Refai MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. M. H. Shahin.

Ethics declarations

Conflict of interest

The authors report no competing interest. The authors alone are responsible for the content and writing of the paper.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Additional information

Redaktion

U. Müller-Ladner, Bad Nauheim

U. Lange, Bad Nauheim

The authors have no financial or proprietary interest in any product mentioned in this paper.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Raafat, I.I., El Guindy, N., Shahin, R.M.H. et al. Toll-like receptor 7 gene single nucleotide polymorphisms and the risk for systemic lupus erythematosus: a case-control study. Z Rheumatol 77, 416–420 (2018). https://doi.org/10.1007/s00393-017-0283-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00393-017-0283-7

Keywords

Schlüsselwörter

Search

Navigation