Gene Is Associated With Lung Function Response to Ivacaftor in Patients With Cystic Fibrosis

Overview

Journal Front Pharmacol

Date 2018 Aug 25

PMID 30140228

Citations 18

Authors

Harriet Corvol

Julie Mesinele

Isman-Hassan Douksieh

Lisa J Strug

Pierre-Yves Boelle

Loic Guillot

Affiliations

Soon will be listed here.

Abstract

Ivacaftor is a drug used to treat cystic fibrosis (CF) patients carrying specific gating mutations. Interpatient variability in the lung response has been shown to be partly explained by rs7512462 in the Solute Carrier Family 26 Member 9 () gene. In an independent and larger cohort, we aimed to evaluate whether variants contribute to the variability of the lung phenotype and if they influence the lung response to ivacaftor. We genotyped the French CF Gene Modifier Study cohort ( = 4,840) to investigate whether variants were involved in the lung phenotype heterogeneity. Their influence in the response to ivacaftor was tested in the 30 treated patients who met the inclusion criteria: older than 6 years of age, percent-predicted forced expiratory volume measured in 1 s (FEV) in the 3 months before treatment initiation ranging between 40 and 90%. Response to treatment was determined by the change in FEV from baseline, averaged in 15-75 days, and the 1st-year post-treatment. We observed that variants were not associated with lung function variability in untreated patients and that gain of lung function in patients treated with ivacaftor was similar to clinical trials. We confirmed that rs7512462 was associated with variability in ivacaftor-lung response, with a significant reduction in lung function improvement for patients with the C allele. Other SNPs also contributed to the ivacaftor-response. Interindividual variability in lung response to ivacaftor is associated with variants in French CF patients. Pharmacogenomics and personalized medicine will soon be part of CF patient care.

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