TY - JOUR
T1 - Synonymous ABCA3 variants do not increase risk for neonatal respiratory distress syndrome
AU - Wambach, Jennifer A.
AU - Wegner, Daniel J.
AU - Heins, Hillary B.
AU - Druley, Todd E.
AU - Mitra, Robi D.
AU - Hamvas, Aaron
AU - Cole, F. Sessions
PY - 2014/6
Y1 - 2014/6
N2 - Objective To determine whether synonymous variants in the adenosine triphosphate-binding cassette A3 transporter (ABCA3) gene increase the risk for neonatal respiratory distress syndrome (RDS) in term and late preterm infants of European and African descent. Study design Using next-generation pooled sequencing of race-stratified DNA samples from infants of European and African descent at 34 weeks gestation with and without RDS (n = 503), we scanned all exons of ABCA3, validated each synonymous variant with an independent genotyping platform, and evaluated race-stratified disease risk associated with common synonymous variants and collapsed frequencies of rare synonymous variants. Results The synonymous ABCA3 variant frequency spectrum differs between infants of European descent and those of African descent. Using in silico prediction programs and statistical strategies, we found no potentially disruptive synonymous ABCA3 variants or evidence of selection pressure. Individual common synonymous variants and collapsed frequencies of rare synonymous variants did not increase disease risk in term and late-preterm infants of European or African descent. Conclusion In contrast to rare, nonsynonymous ABCA3 mutations, synonymous ABCA3 variants do not increase the risk for neonatal RDS among term and late-preterm infants of European or African descent.
AB - Objective To determine whether synonymous variants in the adenosine triphosphate-binding cassette A3 transporter (ABCA3) gene increase the risk for neonatal respiratory distress syndrome (RDS) in term and late preterm infants of European and African descent. Study design Using next-generation pooled sequencing of race-stratified DNA samples from infants of European and African descent at 34 weeks gestation with and without RDS (n = 503), we scanned all exons of ABCA3, validated each synonymous variant with an independent genotyping platform, and evaluated race-stratified disease risk associated with common synonymous variants and collapsed frequencies of rare synonymous variants. Results The synonymous ABCA3 variant frequency spectrum differs between infants of European descent and those of African descent. Using in silico prediction programs and statistical strategies, we found no potentially disruptive synonymous ABCA3 variants or evidence of selection pressure. Individual common synonymous variants and collapsed frequencies of rare synonymous variants did not increase disease risk in term and late-preterm infants of European or African descent. Conclusion In contrast to rare, nonsynonymous ABCA3 mutations, synonymous ABCA3 variants do not increase the risk for neonatal RDS among term and late-preterm infants of European or African descent.
UR - http://www.scopus.com/inward/record.url?scp=84901503604&partnerID=8YFLogxK
U2 - 10.1016/j.jpeds.2014.02.021
DO - 10.1016/j.jpeds.2014.02.021
M3 - Article
C2 - 24657120
AN - SCOPUS:84901503604
SN - 0022-3476
VL - 164
SP - 1316-1321.e3
JO - Journal of Pediatrics
JF - Journal of Pediatrics
IS - 6
ER -