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Polymorphisms on key genes of the inflammatory response in allergic asthma, and their role in cystic fibrosis and severe acute viral bronchiolitis

Fernando Augusto de Lima Marson
Total Authors: 1
Document type: Doctoral Thesis
Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
Defense date:
Examining board members:
Dirceu Solé; Nelson Augusto Rosário Filho; Paulo Augusto Moreira Camargos; Marilda de Souza Gonçalves
Advisor: José Dirceu Ribeiro

Introduction: Genetic variants of genes involved in the inflammatory response act in the presence and/or severity of allergic asthma, cystic fibrosis (CF), severe acute viral bronchiolitis (SAVB). Objective: To describe and verify the associations between clinical and laboratory variables of patients with allergic asthma, CF and SAVB. Comparing the presence and severity of these diseases with the genotype of 251 polymorphisms of 125 genes. Methods: In the present study was enrolled 244 patients with allergic asthma, 273 with CF, 186 with SAVB and 536 healthy controls. The polymorphisms genotypes were achieved by OpenArray technique. Clinical and laboratory data were obtained from medical records of patients, interviews with parents and/or guardians, clinical and/or laboratory tests. The clinical and laboratory markers evaluated were 44, 34 and 32 in allergic asthma, CF and SAVB, respectively. Statistical analysis was performed using SPSS version 22.0 considering ? = 0.05. Results: The presentation of results are described, respectively, by the number of genes and polymorphisms associated to each variable, in parentheses. Allergic asthma: presence of disease (56/79); disease severity (11/12); persistent asthma compared with intermittent (18/20); degree of disease control (16/20); degrees of severity of the disease versus healthy controls [intermittent (35 genes, five unique); mild persistent (39 genes, five unique); moderate persistent (44 genes, three unique); severe persistent (34 genes, eight unique)]; degrees of control of the disease versus healthy controls [uncontrolled (38 genes, five unique); partially controlled (23 genes, three unique); controlled (54 genes, 22 unique); FVC% (14/15); FEV1% (6/7); FVC/FEV1 (12/20); FEF25-75% (12/19); recurrent pneumonia (9/9); body mass index (BMI) (12/14); atopy (19/19); and time of onset of symptoms (14/14). CF: compared with healthy controls (42/53); age of patients (19/42); onset of symptoms (combined and lung disease) (11/13); time for diagnosis (13/14); BMI (24/28); nasal polyposis (10/12); bacteria identification [time to identification for the first Pseudomonas aeruginosa (8/10); presence of mucoid P. aeruginosa (6/8) and non-mucoid P. aeruginosa (11/11); Achromobacter xylosoxidans (9/9); Burkholderia cepacia (8/9) and Staphylococcus aureus (5/5)]; severity scores [Bhalla (10/11), Kanga (15/16) and Shwachman-Kulczcki (17/18 )]; pulmonary function pre-inhaled bronchodilator [SaO2 (9/11), FVC% (10/10), FEV1% (12/13), FEV1/FVC (4/5) and FEF25-75% (7/8)] and lung function post inhaled bronchodilator [FVC% (10/10), FEV1% (12/13), FEV1/FVC (4/5) and FEF25-75% (7/8)]. SAVB: compared with healthy controls (51/65); hospitalization time (6/9); oxygen therapy (4/7); mechanical ventilation (6/6); need for ICU (4/4); identified virus [RSVA (11/14), RSVB (8/10), rhinovirus (12/12) and coinfection (9/10)] and death (4/5). Comparing the genotypic frequency of polymorphisms in the presence of allergic asthma + CF + SAVB, compared to healthy controls there were difference for 47 polymorphisms in 40 different genes; however, when we grouped allergic asthma + SAVB versus healthy controls there was association with 86 polymorphisms in 60 different genes. The descriptive data analysed, associations between clinical and laboratory variables each other, and the association of mutations in the CFTR gene with the markers of severity are not presented in the final abstract. Conclusion: Genetic variants evaluated act in the presence and/or severity of allergic asthma, CF and SAVB. (AU)

FAPESP's process: 11/12939-4 - Association between polymorphisms in modifier genes in children and adolescent with allergic and non-allergic: mild, moderate and severe asthma
Grantee:Fernando Augusto de Lima Marson
Support type: Scholarships in Brazil - Doctorate