Ontology highlight
ABSTRACT: Background
The CFTR modulator ivacaftor has been variably effective in treating individuals with cystic fibrosis (CF) who harbor CFTR gating variants such as G551D, as well as other classes of CFTR variants when used with other modulators. Because CFTR genotype does not fully explain this variability, defining genetic modifiers of response to modulator therapy is of particular interest to the field of individualized CF drug therapy. Previous studies have proposed that a variant in SLC26A9 (rs7512462) is associated with lung disease severity and with response to treatment with ivacaftor in individuals with CF who carry G551D or gating variants.Methods
Given the implications for CF treatment, we re-examined the reported associations in three cohorts; patients enrolled in the Twin and Siblings study at Johns Hopkins University, the CF modifier study at the University of North Carolina at Chapel Hill, and the prospective G551D Observational (GOAL) study. The GOAL study was specifically designed to measure lung function response to ivacaftor.Results
We find no association between SLC26A9 (rs7512462) genotype and lung disease severity (n = 272) or change in lung function at one-, three-, and six-month intervals following ivacaftor treatment(n = 141) in individuals with CF who carry at least one G551D variant.Conclusions
Our inability to replicate this association indicates that rs7512462 genotype should not be used in treatment decisions.
SUBMITTER: Eastman AC
PROVIDER: S-EPMC8410892 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
Eastman Alice C AC Pace Rhonda G RG Dang Hong H Aksit Melis Atalar MA Vecchio-Pagán Briana B Lam Anh-Thu N AN O'Neal Wanda K WK Blackman Scott M SM Knowles Michael R MR Cutting Garry R GR
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 20210302 5
<h4>Background</h4>The CFTR modulator ivacaftor has been variably effective in treating individuals with cystic fibrosis (CF) who harbor CFTR gating variants such as G551D, as well as other classes of CFTR variants when used with other modulators. Because CFTR genotype does not fully explain this variability, defining genetic modifiers of response to modulator therapy is of particular interest to the field of individualized CF drug therapy. Previous studies have proposed that a variant in SLC26A ...[more]