Sheu C C, Zhai R, Su L, Tejera P, Gong M N, Thompson B T, Chen F, Christiani D C
Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
Eur Respir J. 2009 Mar;33(3):543-50. doi: 10.1183/09031936.00091308. Epub 2008 Nov 14.
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.
表皮生长因子（EGF）参与肺泡上皮修复、肺液体清除及炎症反应，并受性激素调控。我们开展了一项非匹配的巢式病例对照研究，以评估EGF基因变异与急性呼吸窘迫综合征（ARDS）的关联，以及性别在EGF基因变异与ARDS关联中的作用。纳入入住重症监护病房时具有ARDS危险因素的患者。病例组为416例发生ARDS的白种人，对照组为1052例未发生ARDS的白种人。对病例组进行临床结局及60天死亡率随访。对一个功能性单核苷酸多态性（SNP）rs4444903以及跨越整个EGF基因的6个标签单核苷酸多态性进行基因分型。在所有受试者中，未发现单个SNP或单倍型与ARDS风险或结局相关。按性别分层分析显示，EGF变异对男性和女性ARDS的影响相反。SNP rs4444903、rs2298991、rs7692976和rs4698803以及单倍型GGCGTC和ATCAAG与男性ARDS风险相关。在女性中未观察到相关性。交互分析显示，rs4444903、rs2298991、rs7692976和rs6533485在ARDS风险方面与性别存在显著交互作用。本研究提示，表皮生长因子基因变异与急性呼吸窘迫综合征风险的关联存在性别差异。目前的研究结果应在其他人群中进行重复验证。
