@article{a6004bd76c444f91b949e265225602f3,
title = "SLC26A9 SNP rs7512462 is not associated with lung disease severity or lung function response to ivacaftor in cystic fibrosis patients with G551D-CFTR",
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.",
keywords = "G551D, Ivacaftor efficacy, Modifier genes, SLC26A9 rs7512462",
author = "Eastman, {Alice C.} and Pace, {Rhonda G.} and Hong Dang and Aksit, {Melis Atalar} and Briana Vecchio-Pag{\'a}n and Lam, {Anh Thu N.} and O'Neal, {Wanda K.} and Blackman, {Scott M.} and Knowles, {Michael R.} and Cutting, {Garry R.}",
note = "Funding Information: The authors would like to thank Chris Dowd, Linh Do, Christopher Penland, and Bruce Marshall at the Cystic Fibrosis Foundation (CFF), Steven Rowe and Jennifer Guimbellot at the University of Alabama, Arthur Baines and Sonya Heltshe at Seattle Children's Hospital, and Jessica Dickerson, Molly Sheridan and Patricia Cornwall at Johns Hopkins Medical Institute. The authors would additionally like to thank the Cystic Fibrosis Foundation for the use of CF Foundation Patient Registry data to conduct this study, as well as the patients, care providers, and clinic coordinators at CF centers throughout the United States for their contributions to the CF Foundation Patient Registry. This study was funded by the NIH through an R01 grant [grant number R01DK044003] as well as two grants from the CFF [grant number CUTTIN18XX0 funding the GOAL project and grant number CUTTIN17G0]. Funding Information: The authors would like to thank Chris Dowd, Linh Do, Christopher Penland, and Bruce Marshall at the Cystic Fibrosis Foundation (CFF), Steven Rowe and Jennifer Guimbellot at the University of Alabama, Arthur Baines and Sonya Heltshe at Seattle Children's Hospital, and Jessica Dickerson, Molly Sheridan and Patricia Cornwall at Johns Hopkins Medical Institute. The authors would additionally like to thank the Cystic Fibrosis Foundation for the use of CF Foundation Patient Registry data to conduct this study, as well as the patients, care providers, and clinic coordinators at CF centers throughout the United States for their contributions to the CF Foundation Patient Registry. This study was funded by the NIH through an R01 grant [grant number R01DK044003 ] as well as two grants from the CFF [grant number CUTTIN18XX0 funding the GOAL project and grant number CUTTIN17G0 ]. Publisher Copyright: {\textcopyright} 2021 European Cystic Fibrosis Society",
year = "2021",
month = sep,
doi = "10.1016/j.jcf.2021.02.007",
language = "English (US)",
volume = "20",
pages = "851--856",
journal = "Journal of Cystic Fibrosis",
issn = "1569-1993",
publisher = "Elsevier",
number = "5",
}