Variants in Solute Carrier SLC26A9 Modify Prenatal Exocrine Pancreatic Damage in Cystic Fibrosis
Published Date:Mar 11 2015
Source:J Pediatr. 166(5):1152-1157.e6.
Cystic Fibrosis Transmembrane Conductance Regulator
Genetic Predisposition To Disease
Immunoreactive Trypsinogen (trypsinogen)
Newborn Screening (neonatal Screening Or Newborn Infant Screening)
Polymorphism, Single Nucleotide
Pubmed Central ID:PMC4530786
Funding:1R01 DK61886-01/DK/NIDDK NIH HHS/United States
DP2 OD007031/OD/NIH HHS/United States
DP20D007031/DP/NCCDPHP CDC HHS/United States
MOP-258916/Canadian Institutes of Health Research/Canada
R01 DK061886/DK/NIDDK NIH HHS/United States
R01 HL068890/HL/NHLBI NIH HHS/United States
R01 HL068890-13/HL/NHLBI NIH HHS/United States
To test the hypothesis that multiple constituents of the apical plasma membrane residing alongside the causal CF Transmembrane Conductance Regulator (CFTR) protein, including known cystic fibrosis (CF) modifiers SLC26A9, SLC6A14, and SLC9A3, would be associated with prenatal exocrine pancreatic damage as measured by newborn screened (NBS) IRT levels.
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 eight SNPs in SLC26A9, SLC6A14 and SLC9A3 were associated with IRT and whether other constituents of the apical plasma membrane contributed to IRT.
In the Colorado sample, three SLC26A9 SNPs were associated with NBS IRT (min P = 1.16 × 10−3; rs7512462), but no SLC6A14 or SLC9A3 SNPs were associated (P > 0.05). The rs7512462 association replicated in the Wisconsin sample (P = 0.03) but not in the French sample (P = 0.76). Furthermore, rs7512462 was the top ranked apical membrane constituent in the combined Colorado and Wisconsin sample.
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 suggests SLC26A9 as a potential therapeutic target to ameliorate exocrine pancreatic disease.
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