Genetics and Molecular Biology (Mar 2024)

Association between cystic fibrosis transmembrane regulator genotype and clinical outcomes, glucose homeostasis indices and CF-related diabetes risk in adults with CF

  • Noémie Bélanger,
  • Anne Bonhoure,
  • Tamizan Kherani,
  • Valérie Boudreau,
  • François Tremblay,
  • Annick Lavoie,
  • Maite Carricart,
  • Ashish Marwaha,
  • Rémi Rabasa-Lhoret,
  • Kathryn J. Potter

DOI
https://doi.org/10.1590/1678-4685-gmb-2023-0021
Journal volume & issue
Vol. 47, no. 1

Abstract

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Abstract People living with cystic fibrosis (pwCF) homozygous for F508del present more severe phenotypes. PwCF with compound heterozygous genotypes F508del /A455E and F508del /L206W may have milder cystic fibrosis (CF) phenotypes. We compared F508del homozygotes and common compound heterozygotes (F508del and a second pathogenic variant) in adult patients. Nutritional, pulmonary function and glucose homeostasis indices data were collected from the prospective Montreal CF cohort. Two-hundred and three adults with CF having at least one F508del variant were included. Individuals were divided into subgroups: homozygous F508del/F508del (n=149); F508del/621+1G>T (n=17); F508del/711+1G>T (n=11); F508del/A455E (n=12); and F508del/L206W (n=14). Subgroups with the F508del/L206W and F508del/A455E had a lower proportion with pancreatic exocrine insufficiency (p<0.0001), a higher fat mass (p<0.0001), and lower glucose area under the curve (AUC) (p=0.027). The F508del/L206W subgroup had significantly higher insulin secretion (AUC; p=0.027) and body mass index (p<0.001). Pulmonary function (FEV1) was significantly higher for the F508del/L206W subgroup (p<0.0001). Over a median of 7.37 years, the risk of developing CFRD in 141 patients was similar between groups. PwCF with heterozygous F508del/L206W and F508del/A455E tended to have pancreatic exocrine sufficiency, better nutritional status, improved pulmonary function and better diabetogenic indices, but this does not translate into lower risk of CF-related Diabetes.

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