@article{fcc06dc38c764f0c8ab81f55e0e8f11d,
title = "Variants in solute carrier SLC26A9 modify prenatal exocrine pancreatic damage in cystic fibrosis",
abstract = "Objectives To test the hypothesis that multiple constituents of the apical plasma membrane residing alongside the causal cystic fibrosis (CF) transmembrane conductance regulator protein, including known CF modifiers SLC26A9, SLC6A14, and SLC9A3, would be associated with prenatal exocrine pancreatic damage as measured by newborn screened (NBS) immunoreactive trypsinogen (IRT) levels. Study design NBS IRT measures and genome-wide genotype data were available on 111 subjects from Colorado, 37 subjects from Wisconsin, and 80 subjects from France. Multiple linear regression was used to determine whether any of 8 single nucleotide polymorphisms (SNPs) in SLC26A9, SLC6A14, and SLC9A3 were associated with IRT and whether other constituents of the apical plasma membrane contributed to IRT. Results In the Colorado sample, 3 SLC26A9 SNPs were associated with NBS IRT (min P = 1.16 × 10-3; rs7512462), but no SLC6A14 or SLC9A3 SNPs were associated (P >.05). The rs7512462 association replicated in the Wisconsin sample (P =.03) but not in the French sample (P =.76). Furthermore, rs7512462 was the top-ranked apical membrane constituent in the combined Colorado and Wisconsin sample. Conclusions NBS IRT is a biomarker of prenatal exocrine pancreatic disease in patients with CF, and a SNP in SLC26A9 accounts for significant IRT variability. This work suggests SLC26A9 as a potential therapeutic target to ameliorate exocrine pancreatic disease.",
author = "Miller, {Melissa R.} and David Soave and Weili Li and Jiafen Gong and Pace, {Rhonda G.} and Bo{\"e}lle, {Pierre Yves} and Cutting, {Garry R.} and Drumm, {Mitchell L.} and Knowles, {Michael R.} and Lei Sun and Rommens, {Johanna M.} and Frank Accurso and Durie, {Peter R.} and Harriet Corvol and Hara Levy and Sontag, {Marci K.} and Strug, {Lisa J.}",
note = "Funding Information: Funded by the Canadian Institutes of Health Research ( MOP-258916 [to L.S.]), Cystic Fibrosis Canada (2626 [to L.S.]), the National Institutes of Health/ National Heart, Lung, and Blood Institute ( R01 HL068890-13 [to M.K.] and DP20D007031 [to H.L.]), National Institute of Diabetes and Digestive and Kidney Diseases ( 1RO1 DK61886-01 [to F.A.]), the Children's Hospital of Wisconsin Research Institute (to H.L.), and the United States Cystic Fibrosis Foundation ( Sontag07AO and Miller13A0 ). Funds for genome-wide genotyping of North American participants were generously provided by the United States Cystic Fibrosis Foundation . H.C. and P.-Y.B. are supported by the Institut national de la sant{\'e} et de la recherche m{\'e}dicale , Assistance Publique H{\^o}pitaux de Paris , Universit{\'e} Pierre et Marie Curie Paris , Agence Nationale de la Recherche ( R09186DS ), DGS , Association Vaincre La Mucoviscidose , Chancellerie des Universit{\'e}s (Legs Poix), Association Agir Informer Contre la Mucoviscidose , and GIS-Institut des Maladies Rares . M.M., W.L., and D.S. are fellows of the CIHR Strategic Training for Advanced Genetic Epidemiology and Statistical Genetics. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = may,
day = "1",
doi = "10.1016/j.jpeds.2015.01.044",
language = "English (US)",
volume = "166",
pages = "1152--1157.e6",
journal = "Journal of Pediatrics",
issn = "0022-3476",
publisher = "Mosby Inc.",
number = "5",
}