title: IL8 gene as modifier of cystic fibrosis: unraveling the factors which influence clinical variability.
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.
authors.affiliation: 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.
authors.forename: Larissa Lazzarini
authors.initials: LL
authors.lastname: Furlan
authors.affiliation: 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. fernandolimamarson@hotmail.com.|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. fernandolimamarson@hotmail.com.
authors.forename: Fernando Augusto Lima
authors.initials: FA
authors.lastname: Marson
authors.affiliation: 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.
authors.forename: José Dirceu
authors.initials: JD
authors.lastname: Ribeiro
authors.affiliation: 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.
authors.forename: Carmen Sílvia
authors.initials: CS
authors.lastname: Bertuzzo
authors.affiliation: 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.
authors.forename: João Batista
authors.initials: JB
authors.lastname: Salomão Junior
authors.affiliation: 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.
authors.forename: Dorotéia Rossi Silva
authors.initials: DR
authors.lastname: Souza
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000235:genetics* / Q000382:microbiology / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006454:Hemoglobins / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000382:microbiology / Q000503:physiopathology; D016209:Interleukin-8 / Q000235:genetics*; D008171:Lung Diseases / Q000235:genetics* / Q000382:microbiology / Q000503:physiopathology; D008297:Male; D010100:Oxygen / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011552:Pseudomonas Infections / Q000235:genetics / Q000382:microbiology / Q000503:physiopathology; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity; D012720:Severity of Illness Index
chemical_list: C505032:CFTR protein, human; C508606:CXCL8 protein, human; D006454:Hemoglobins; D016209:Interleukin-8; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D010100:Oxygen