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Citations to this article

Increased expression of anion transporter SLC26A9 delays diabetes onset in cystic fibrosis
Anh-Thu N. Lam, … , Scott M. Blackman, Garry R. Cutting
Anh-Thu N. Lam, … , Scott M. Blackman, Garry R. Cutting
Published October 3, 2019
Citation Information: J Clin Invest. 2020;130(1):272-286. https://doi.org/10.1172/JCI129833.
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Research Article Endocrinology Genetics Article has an altmetric score of 5

Increased expression of anion transporter SLC26A9 delays diabetes onset in cystic fibrosis

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Abstract

Diabetes is a common complication of cystic fibrosis (CF) that affects approximately 20% of adolescents and 40%–50% of adults with CF. The age at onset of CF-related diabetes (CFRD) (marked by clinical diagnosis and treatment initiation) is an important measure of the disease process. DNA variants associated with age at onset of CFRD reside in and near SLC26A9. Deep sequencing of the SLC26A9 gene in 762 individuals with CF revealed that 2 common DNA haplotypes formed by the risk variants account for the association with diabetes. Single-cell RNA sequencing (scRNA-Seq) indicated that SLC26A9 is predominantly expressed in pancreatic ductal cells and frequently coexpressed with CF transmembrane conductance regulator (CFTR) along with transcription factors that have binding sites 5′ of SLC26A9. These findings were replicated upon reanalysis of scRNA-Seq data from 4 independent studies. DNA fragments derived from the 5′ region of SLC26A9-bearing variants from the low-risk haplotype generated 12%–20% higher levels of expression in PANC-1 and CFPAC-1 cells compared with the high- risk haplotype. Taken together, our findings indicate that an increase in SLC26A9 expression in ductal cells of the pancreas delays the age at onset of diabetes, suggesting a CFTR-agnostic treatment for a major complication of CF.

Authors

Anh-Thu N. Lam, Melis A. Aksit, Briana Vecchio-Pagan, Celeste A. Shelton, Derek L. Osorio, Arianna F. Anzmann, Loyal A. Goff, David C. Whitcomb, Scott M. Blackman, Garry R. Cutting

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Total citations by year

Year: 2024 2023 2022 2021 2020 2019 Total
Citations: 1 6 9 6 2 3 27
Citation information
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Citations to this article (27)

Title and authors Publication Year
Impact of Gene Modifiers on Cystic Fibrosis Phenotypic Profiles: A Systematic Review
Ward A, Mauleon R, Ooi CY, Rosic N
Human Mutation 2024
SLC26A9 in airways and intestine: secretion or absorption?
Kunzelmann K, Centeio R, Ousingsawat J, Talbi K, Seidler U, Schreiber R
Channels (Austin, Tex.) 2023
Single-Cell RNA Sequencing Reveals New Basic and Translational Insights in the Cystic Fibrosis Lung.
Januska MN, Walsh MJ
American journal of respiratory cell and molecular biology 2023
Cystic Fibrosis–Related Diabetes Workshop: Research Priorities Spanning Disease Pathophysiology, Diagnosis, and Outcomes
Putman MS, Norris AW, Hull RL, Rickels MR, Sussel L, Blackman SM, Chan CL, Ode KL, Daley T, Stecenko AA, Moran A, Helmick MJ, Cray S, Alvarez JA, Stallings VA, Tuggle KL, Clancy JP, Eggerman TL, Engelhardt JF, Kelly A
Diabetes 2023
Cystic Fibrosis-Related Diabetes Workshop: Research Priorities Spanning Disease Pathophysiology, Diagnosis, and Outcomes.
Putman MS, Norris AW, Hull RL, Rickels MR, Sussel L, Blackman SM, Chan CL, Ode KL, Daley T, Stecenko AA, Moran A, Helmick MJ, Cray S, Alvarez JA, Stallings VA, Tuggle KL, Clancy JP, Eggerman TL, Engelhardt JF, Kelly A
Diabetes care 2023
New discoveries in the field of metabolism by applying single-cell and spatial omics
Xie B, Gao D, Zhou B, Chen S, Wang L
Journal of Pharmaceutical Analysis 2023
Pathogenic Relationships in Cystic Fibrosis and Renal Diseases: CFTR, SLC26A9 and Anoctamins
Kunzelmann K, Ousingsawat J, Kraus A, Park JH, Marquardt T, Schreiber R, Buchholz B
International journal of molecular sciences 2023
SLC26A9 as a Potential Modifier and Therapeutic Target in Cystic Fibrosis Lung Disease
G Gorrieri, F Zara, P Scudieri
Biomolecules 2022
The role of genetic modifiers, inflammation and CFTR in the pathogenesis of Cystic fibrosis related diabetes
S Hasan, S Soltman, C Wood, SM Blackman
Journal of Clinical & Translational Endocrinology 2022
Diabetes and Its Cardiovascular Complications: Comprehensive Network and Systematic Analyses
H Wu, V Norton, K Cui, B Zhu, S Bhattacharjee, Y Lu, B Wang, D Shan, S Wong, Y Dong, S Chan, D Cowan, J Xu, D Bielenberg, C Zhou, H Chen
Frontiers in Cardiovascular Medicine 2022
Genetic evidence supports the development of SLC26A9 targeting therapies for the treatment of lung disease
J Gong, G He, C Wang, C Bartlett, N Panjwani, S Mastromatteo, F Lin, K Keenan, J Avolio, A Halevy, M Shaw, M Esmaeili, G Côté-Maurais, D Adam, S Bégin, C Bjornson, M Chilvers, J Reisman, A Price, M Parkins, R van Wylick, Y Berthiaume, L Bilodeau, D Mateos-Corral, D Hughes, M Smith, N Morrison, J Brusky, E Tullis, A Stephenson, B Quon, P Wilcox, W Leung, M Solomon, L Sun, E Brochiero, T Moraes, T Gonska, F Ratjen, J Rommens, L Strug
npj Genomic Medicine 2022
Pleiotropic modifiers of age-related diabetes and neonatal intestinal obstruction in cystic fibrosis.
Aksit MA, Ling H, Pace RG, Raraigh KS, Onchiri F, Faino AV, Pagel K, Pugh E, Stilp AM, Sun Q, Blue EE, Wright FA, Zhou YH, Bamshad MJ, Gibson RL, Knowles MR, Cutting GR, Blackman SM
The American Journal of Human Genetics 2022
Modifier Factors of Cystic Fibrosis Phenotypes: A Focus on Modifier Genes
Mésinèle J, Ruffin M, Guillot L, Corvol H
International journal of molecular sciences 2022
Physiology and pathophysiology of human airway mucus
Hill DB, Button B, Rubinstein M, Boucher RC
Physiological reviews 2022
ISPAD Clinical Practice Consensus Guidelines 2022: Management of cystic fibrosis‐related diabetes in children and adolescents
Ode KL, Ballman M, Battezzati A, Brennan A, Chan CL, Hameed S, Ismail HM, Kelly A, Moran AM, Rabasa\u2010Lhoret R, Saxby NA, Craig ME
Pediatric Diabetes 2022
Endocrine Complications of Cystic Fibrosis
Kelly A, Marks BE, Stalvey MS
Clinics in Chest Medicine 2022
Cystic Fibrosis-Related Diabetes (CFRD): Overview of Associated Genetic Factors
F Iafusco, G Maione, FM Rosanio, E Mozzillo, A Franzese, N Tinto
Diagnostics 2021
The Potential Causes of Cystic Fibrosis-Related Diabetes
L Coderre, L Debieche, J Plourde, R Rabasa-Lhoret, S Lesage
Frontiers in Endocrinology 2021
SLC26A9 SNP rs7512462 is not associated with lung disease severity or lung function response to ivacaftor in cystic fibrosis patients with G551D-CFTR
AC Eastman, RG Pace, H Dang, MA Aksit, B Vecchio-Pagán, AT Lam, WK O'Neal, SM Blackman, MR Knowles, GR Cutting
Journal of Cystic Fibrosis 2021
Pharmacological Modulation of Ion Channels for the Treatment of Cystic Fibrosis
MC Pinto, IA Silva, MF Figueira, MD Amaral, M Lopes-Pacheco
Journal of Experimental Pharmacology 2021
Synergy in Cystic Fibrosis Therapies: Targeting SLC26A9
MC Pinto, MC Quaresma, IA Silva, V Railean, SS Ramalho, MD Amaral
International journal of molecular sciences 2021
Cystic fibrosis being a polyendocrine disease (Review)
N Chagay, G Khayt, T Vdovina, A Shaforost
Problems of Endocrinology 2021
Precision medicine for pancreatic diseases
CA Shelton, DC Whitcomb
Current Opinion in Gastroenterology 2020
Genetic Variation Near chrXq22-q23 Is Linked to Emotional Functioning in Cystic Fibrosis
E Barbato, B Daly, S Douglas, M Kerr, P Litman, R Darrah
Biological research for nursing 2020
Genetic Modifiers of Cystic Fibrosis-Related Diabetes Have Extensive Overlap With Type 2 Diabetes and Related Traits
MA Aksit, RG Pace, B Vecchio-Pagán, H Ling, JM Rommens, PY Boelle, L Guillot, KS Raraigh, E Pugh, P Zhang, LJ Strug, ML Drumm, MR Knowles, GR Cutting, H Corvol, SM Blackman
The Journal of clinical endocrinology and metabolism 2019
The genetics and genomics of cystic fibrosis
N Sharma, GR Cutting
Journal of Cystic Fibrosis 2019
Genetic variation in CFTR and modifier loci may modulate cystic fibrosis disease severity
A Paranjapye, M Ruffin, A Harris, H Corvol
Journal of Cystic Fibrosis 2019

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