Variants in Solute CarrierSLC26A9Modify Prenatal Exocrine Pancreatic Damage in Cystic Fibrosis
Melissa R. Miller, David Soave, Weili Li,Johanna M. Rommens
DOI:
http://dx.doi.org/10.1016/j.jpeds.2015.01.044 Abstract
Objectives
To test the hypothesis that multiple constituents of the apical plaa membrane residing alongside the causal cystic fibrosis (CF) tranembrane conductance regulator protein, including known CF modifiersSLC26A9,SLC6A14, andSLC9A3, 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 polymorphis (SNPs) inSLC26A9,SLC6A14, andSLC9A3were associated with IRT and whether other constituents of the apical plaa membrane contributed to IRT.
Results
In the Colorado sample, 3SLC26A9SNPs were associated with NBS IRT (minP= 1.16×10−3; rs7512462), but noSLC6A14orSLC9A3SNPs 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 inSLC26A9accounts for significant IRT variability. This work suggestsSLC26A9as a potential therapeutic target to ameliorate exocrine pancreatic disease.
