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IL8 gene as modifier of cystic fibrosis: unraveling the factors which influence clinical variability

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An Erratum to this article was published on 03 February 2017

Abstract

The severity of cystic fibrosis (CF) is associated with classes of mutations in the CFTR gene (cystic fibrosis transmembrane regulator), physical environment and modifier genes interaction. The IL8 gene (interleukin 8), according to its respective polymorphisms, influences inflammatory responses. This study analyzed IL8 gene polymorphisms (rs4073, rs2227306 and rs2227307), by means of PCR/RFLP, and their association with pulmonary function markers and clinical severity scores in 186 patients with CF, considering the CFTR genotype. There was an association between rs2227307 and precocity of the disease. The severity of lung disease was associated with the following markers: transcutaneous arterial hemoglobin oxygen saturation (SaO2) (regardless of CFTR genotype, for the polymorphisms rs4073, rs2227306 and rs2227307); mucoid Pseudomonas aeruginosa (regardless of CFTR genotype, for the polymorphisms rs2227306 and rs2227307). Pulmonary function markers (SaO2 and spirometric variables) and clinical severity scores were also associated with IL8 gene polymorphisms. This study identified the IL8 gene, represented by rs4073 and rs2227306 polymorphisms, and particularly the rs2227307 polymorphism, as potentiating factors for the degree of variability in the severity of CF, especially in pulmonary clinical manifestation correlated with increased morbidity and mortality.

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Acknowledgments

FALM: financial support from the following institutions: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), for sponsoring the researches #2011/12939-4 and #2015/12858-5; Fundo de Apoio à Pesquisa ao Ensino e à Extensão da Universidade Estadual de Campinas, for sponsoring the research #0648/2015; JDR: FAPESP, for sponsoring the research #2011/18845-1; LLF: FAPESP, for sponsoring the research #2013/19052-0. Luciana Montes Rezende, Luciana Cardoso Bonadia and Stephanie Villa-Nova for their technical support during DNA extraction and identification of mutations of the CFTR gene. Marcela Augusta de Souza Pinhel, Michele Lima Gregório, Rafael Fernandes Ferreira, Graciele Domitila Tenani and Heloisa Cristina Caldas for their technical support during standardization of IL-8 genotyping. Maria Ângela Gonçalves de Oliveira Ribeiro for conducting pulmonary function tests (LAFIP/Ciped/Unicamp). Rafaella Maionchi Pereira Martins for her technical support to determine clinical scores. Maria de Fátima Corrêa Pimenta Servidoni for promoting a link between both Universities. Carlos Emilio Levy for the microbiological analysis of respiratory airway secretion.

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    Authors and Affiliations

    1. Medical School of São José do Rio Preto, Avenida Brigadeiro Faria Lima, 5416, Vila São José, São José do Rio Preto, São Paulo, CEP 15090-000, Brazil

      Larissa Lazzarini Furlan

    2. Department of Medical Genetics, School of Medical Sciences, University of Campinas, Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, CEP 13083-887, Brazil

      Fernando Augusto Lima Marson & Carmen Sílvia Bertuzzo

    3. Department of Pediatrics, School of Medical Sciences, University of Campinas, Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, CEP 13083-887, Brazil

      Fernando Augusto Lima Marson & José Dirceu Ribeiro

    4. Department of Pediatrics and Department of Pediatrics Pneumology, University Hospital, Medical School of São José do Rio Preto, Avenida Brigadeiro Faria Lima, 5416, Vila São José, São José do Rio Preto, São Paulo, CEP 15090-000, Brazil

      João Batista Salomão Junior

    5. Department of Molecular Biology, Research Center for Biochemistry and Molecular Biology, Medical School of São José do Rio Preto, Avenida Brigadeiro Faria Lima, 5416, Vila São José, São José do Rio Preto, São Paulo, CEP 15090-000, Brazil

      Dorotéia Rossi Silva Souza

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    L. L. Furlan and F. A. L. Marson contributed equally to this work.

    An erratum to this article is available at http://dx.doi.org/10.1007/s00439-017-1761-3.

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    Furlan, L.L., Marson, F.A.L., Ribeiro, J.D. et al. IL8 gene as modifier of cystic fibrosis: unraveling the factors which influence clinical variability. Hum Genet 135, 881–894 (2016). https://doi.org/10.1007/s00439-016-1684-4

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