Pharmacogenetics and genomics · 2026
CFTR genotype-phenotype associations and clinical outcomes in pediatric cystic fibrosis.
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Arpini Luana da Silva Baptista, Liberato Fernanda Mayrink Gonçalves, Santos Sabrina da Silva, Monteiro Gina Torres Rego
Аннотация
OBJECTIVE: To investigate the association between CFTR genotypes and clinical and nutritional outcomes in children and adolescents with cystic fibrosis (CF) receiving care within the public health system of Espírito Santo, Brazil.
METHODS: This cross-sectional study retrospectively analyzed clinical and genetic data from 110 individuals under 18 years with confirmed CF, followed at a state reference center between 2007 and 2024. CFTR variants were classified by functional consequence and grouped by severity. Outcomes included pancreatic insufficiency, forced expiratory volume in 1 s (FEV1%), Shwachman-Kulczycki score, nutritional status, and chronic airway colonization by Pseudomonas aeruginosa . Associations were assessed using appropriate statistical tests.
RESULTS: A high degree of CFTR genotypic heterogeneity was observed, with predominance of the F508del variant (72.7%) alongside a substantial proportion of non-F508del and rare pathogenic variants. Individuals carrying two class I-III variants had a higher frequency of pancreatic insufficiency ( P = 0.026). The presence of p.Phe508del was associated with worse pulmonary function ( P = 0.031) and bone demineralization ( P = 0.026). The Shwachman-Kulczycki score correlated negatively with age and age at diagnosis and positively with BMI z -score and FEV1%. No significant associations were found between genotype and chronic P. aeruginosa colonization, liver disease, or overall disease severity.
CONCLUSION: CFTR genotypic heterogeneity was high, with minimal function variants associated with poorer clinical outcomes. The notable presence of rare variants underscores the need for regional studies to better characterize phenotypic variability and support precision medicine strategies in middle-income settings.
METHODS: This cross-sectional study retrospectively analyzed clinical and genetic data from 110 individuals under 18 years with confirmed CF, followed at a state reference center between 2007 and 2024. CFTR variants were classified by functional consequence and grouped by severity. Outcomes included pancreatic insufficiency, forced expiratory volume in 1 s (FEV1%), Shwachman-Kulczycki score, nutritional status, and chronic airway colonization by Pseudomonas aeruginosa . Associations were assessed using appropriate statistical tests.
RESULTS: A high degree of CFTR genotypic heterogeneity was observed, with predominance of the F508del variant (72.7%) alongside a substantial proportion of non-F508del and rare pathogenic variants. Individuals carrying two class I-III variants had a higher frequency of pancreatic insufficiency ( P = 0.026). The presence of p.Phe508del was associated with worse pulmonary function ( P = 0.031) and bone demineralization ( P = 0.026). The Shwachman-Kulczycki score correlated negatively with age and age at diagnosis and positively with BMI z -score and FEV1%. No significant associations were found between genotype and chronic P. aeruginosa colonization, liver disease, or overall disease severity.
CONCLUSION: CFTR genotypic heterogeneity was high, with minimal function variants associated with poorer clinical outcomes. The notable presence of rare variants underscores the need for regional studies to better characterize phenotypic variability and support precision medicine strategies in middle-income settings.