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Association between TLR2/TLR4 gene polymorphisms and COPD phenotype in a Greek cohort

Assoziation zwischen TLR2-/TLR4-Gen-Polymorphismen und COPD-Phänotyp

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Abstract

Background

Considering that the innate immune system plays a pivotal role in the pathogenesis of chronic obstructive pulmonary disease (COPD), we hypothesized that functional single-nucleotide polymorphisms (SNPs) of innate immune genes affect the disease phenotype and prognosis.

Aim

To elucidate the contribution of common functional TLR2 and TLR4 SNPs and genotypic deficiency of the mannose-binding lectin (MBL) protein, both as single parameters and in combination, in Greek COPD patients.

Results

In a cohort of 114 Greek COPD patients, we confirmed that the presence of TLR4-D299G or TLR4-T399I SNPs was significantly associated with an earlier COPD stage (p = 0.003 and p = 0.009, respectively). In comparison, the absence of any analyzed polymorphism, including those of TLR2-R753Q and genotypic MBL deficiency, was significantly associated with a more severe disease phenotype, characterized by more frequent exacerbations (p = 0.045).

Conclusion

Our findings support the notion that the presence of innate immune SNPs, such as functional polymorphisms of TLRs along with MBL deficiency, might exert a protective effect on the COPD phenotype, similar with other immune-mediated disorders.

Zusammenfassung

Hintergrund

Das System der angeborenen Immunität spielt eine entscheidende Rolle bei der Pathogenese der chronisch obstruktiven Lungenerkrankung (COPD). Die Autoren stellten die Hypothese auf, dass funktionelle Polymorphismen („single nucleotide polymorphisms“; SNPs) von Genen des angeborenen Immunsystems Einfluss auf den Erkrankungsphänotyp und der Prognose der COPD haben.

Ziel

Ziel war die Untersuchung der Beteiligung von funktionellen TLR2- und TLR4-SNPs des Toll-like-Rezeptors einerseits und des genotypischen Mangels an MBL-Protein (mannosebindendes Lektin) andererseits, sowohl als singuläre Parameter und in Kombination, bei griechischen COPD-Patienten.

Ergebnisse

In einer Kohorte von n = 114 griechischen COPD-Patienten bestätigten die Autoren die signifikante Assoziation von TLR4-D299G- (p = 0,003) oder TLR4-T399I- (p = 0,009) Polymorphismen mit den frühen Stadien der COPD. Im Gegensatz hierzu war das Fehlen der untersuchten Polymorphismen, inklusive des TLR2-R753Q-Polymorphismus und des genotypischen MBL-Mangels, mit einem ungünstigen Erkrankungsphänotyp mit signifikant (p = 0,045) vermehrten COPD-Exazerbationen assoziiert.

Schlussfolgerung

Die vorliegenden Ergebnisse unterstützen die Auffassung, dass SNPs von Genen der angeborenen Immunität, wie funktionelle Polymorphismen von TLR und der genotypische MBL-Mangel, protektive Effekte auf den COPD-Phänotyp haben könnten, ähnlich wie bei weiteren immunvermittelten Erkrankungen.

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Acknowledgements

The authors would like to thank Ms. Evangelia Karamouti for her excellent technical assistance.

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Authors and Affiliations

  1. School of Health Sciences, Faculty of Medicine, Department of Immunology & Histocompatibility, University of Thessaly, 41500, Larissa, Greece

    A. Apostolou, A. Michopoulos, A. E. Germenis & M. Speletas

  2. School of Health Sciences, Faculty of Medicine, Respiratory Department, University of Thessaly, Larissa, Greece

    T. Kerenidi & K. I. Gourgoulianis

  3. Department of Cardiology, Pneumology and Intensive Care Medicine, Clinic for Internal Medicine I, University Hospital Jena, Friedrich-Schiller-University, Jena, Germany

    M. Noutsias

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  1. A. Apostolou
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Corresponding author

Correspondence to M. Speletas.

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Conflict of interest

M. Noutsias received presentation honoraria by Applied Biosystems, Bayer, and Novartis. A. Apostolou, T. Kerenidi, A. Michopoulos, K.I. Gourgoulianis, A.E. Germenis, and M. Speletas declare that they have no competing interests related to this study.

The study was conducted in accordance with the principles of the Helsinki Declaration and was approved by the Institutional Review Board of the University Hospital of Larissa, Greece.

Additional information

Author contributions. A. Apostolou and A. Michopoulos performed the experiments; T. Kerenidi and K.I. Gourgoulianis provided patients’ samples and clinical data; A.E. Germenis provided reagents and intellectual input; T. Kerenidi and M. Speletas analyzed the data; M. Noutsias was involved in writing and editing the manuscript; M. Speletas designed the study, supervised the experiments, and wrote the manuscript. All authors reviewed and approved the final manuscript.

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Apostolou, A., Kerenidi, T., Michopoulos, A. et al. Association between TLR2/TLR4 gene polymorphisms and COPD phenotype in a Greek cohort. Herz 42, 752–757 (2017). https://doi.org/10.1007/s00059-016-4510-9

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  • DOI: https://doi.org/10.1007/s00059-016-4510-9

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