Associação entre as características fenotípicas, genotípicas e a gravidade da doença em indivíduos com fibrose cística

Abstract

Introduction: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. The relationship between genotype and phenotype in CF is still unclear due to the heterogeneity of mutations, which vary according to geographic origin and ethnicity, and clinical manifestations. Objectives: To analyze the association between phenotypic, genotypic characteristics and the severity of the disease in individuals with cystic fibrosis treated at a Reference Center in Minas Gerais/Brazil. Methods: This is a retrospective study. Anthropometric data, age, sex, age at diagnosis, colonization, respiratory and gastrointestinal manifestations, complications, type of treatment, Shwachman-Kulczycki score and mutations, were collected from the participants' medical records. Nutritional status was analyzed according to the growth curve of the World Health Organization (WHO). Results: The sample included 50 participants, from 1 to 33 years old, 50% of whom were female. The majority (40%) had colonization by Staphylococcus aureus. Of the total 100 alleles of the CFTR gene, the most prevalent mutations were Delta F508 (45%) and S4X (18%). The groups of prevalent mutations showed a significant association (p = 0.013) with pancreatic insufficiency, the same was not observed regarding respiratory symptoms (p = 0.666) and the severity of the disease (p = 0.073). The severity of the disease had a significant association with colonization by Pseudomonas aeruginosa and Staphylococcus aureus (p = 0.007) and with low weight (p = 0.036). The occurrence of death was associated with age at diagnosis (p = 0.016), respiratory symptoms (p = 0.013), colonization (p = 0.024), low weight (p = 0.017) and the occurrence of hospitalization (p = 0.003). Conclusions: It was possible to observe an association between mutations with the presence of pancreatic insufficiency; between colonization by Staphylococcus aureus and low weight with the severity of the disease and the lack of association between mutations and the severity of the disease. The environmental factors deserve to be investigated in more detail, as they seem to have an important impact with the gravity of the disease.