RT Journal Article
SR Electronic
T1 Sex-specific association of epidermal growth factor gene polymorphisms with acute respiratory distress syndrome
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 543
OP 550
DO 10.1183/09031936.00091308
VO 33
IS 3
A1 C. C. Sheu
A1 R. Zhai
A1 L. Su
A1 P. Tejera
A1 M. N. Gong
A1 B. T. Thompson
A1 F. Chen
A1 D. C. Christiani
YR 2009
UL http://erj.ersjournals.com/content/33/3/543.abstract
AB Epidermal growth factor (EGF) is involved in alveolar epithelial repair, lung fluid clearance and inflammation, and is regulated by sex hormones. An unmatched, nested case–control study was conducted to evaluate the associations of EGF variants with acute respiratory distress syndrome (ARDS) and the role of sex on the associations between EGF variants and ARDS. Patients with ARDS risk factors upon intensive care unit admission were enrolled. Cases were 416 Caucasians who developed ARDS and controls were 1,052 Caucasians who did not develop ARDS. Cases were followed for clinical outcomes and 60-day mortality. One functional single nucleotide polymorphism (SNP), rs4444903, and six haplotype-tagging SNPs spanning the entire EGF gene were genotyped. No individual SNP or haplotype was associated with ARDS risk or outcomes in all subjects. Sex-stratified analyses showed opposite effects of EGF variants on ARDS in males versus in females. SNPs rs4444903, rs2298991, rs7692976 and rs4698803, and haplotypes GGCGTC and ATCAAG were associated with ARDS risk in males. No associations were observed in females. Interaction analysis showed that rs4444903, rs2298991, rs7692976 and rs6533485 significantly interacted with sex for ARDS risk. The present study suggests that associations of epidermal growth factor gene variants with acute respiratory distress syndrome risk are modified by sex. The current findings should be replicated in other populations.