Qingdao University, Qingdao, PR China; Department of Respiratory Diseases, Weifang People's Hospital, Weifang, PR China.
Department of Respiratory Diseases, Weifang People's Hospital, Weifang, PR China.
Kaohsiung J Med Sci. 2017 Sep;33(9):433-441. doi: 10.1016/j.kjms.2017.05.014. Epub 2017 Jul 5.
Accumulated data over the years have suggested that hypoxia inducible factor-1 alpha (HIF-1α) and its downstream vascular endothelial growth factor (VEGF) gene may be linked with chronic obstructive pulmonary disease (COPD). This study aims to investigate the association of HIF-1α and VEGF genetic polymorphisms and their correlated risks with COPD. COPD patients (case group) and healthy individuals (control group) were recruited. DNA was extracted to detect HIF-1α and VEGF genetic polymorphisms. Basal lung volume and forced expiratory capacity in 1st second (FEV1)/forced vital capacity (FVC) and FEV/predicted value (pred)% were calculated. Genotype and allele distributions in HIF-1α and VEGF genes were analyzed. Kaplan-Meier curves and logistic regression model were used for analysis of survival and COPD risk factors. Haplotypes for HIF-1α rs11549465 and rs11549467 were analyzed. FEV/FVC and FEV1/pred% in the case group were lower than the control group. Frequencies of HIF-1α rs11549465 CT + TT genotype and T allele, and rs11549467 GA + AA genotype and A allele were higher in the case group than the control group. Patients with rs11549465 CT + TT had higher COPD risk than those with the CC genotype. Patients with rs11549467 GA + AA showed higher COPD risk and lower FEV/FVC and FEV/pred% than those with the GG genotype. Patients with HIF-1α TA haplotype showed higher COPD risk than those with the CG haplotype. Survival rate of patients with HIF-1α rs11549467 GG genotype was higher than those with the GA + AA genotype. HIF-1α rs11549467 polymorphism may be associated with COPD risk.
多年来的积累数据表明，缺氧诱导因子-1 阿尔法（HIF-1α）及其下游血管内皮生长因子（VEGF）基因可能与慢性阻塞性肺疾病（COPD）有关。本研究旨在探讨 HIF-1α 和 VEGF 基因遗传多态性及其相关风险与 COPD 的关系。招募了 COPD 患者（病例组）和健康个体（对照组）。提取 DNA 以检测 HIF-1α 和 VEGF 基因的遗传多态性。计算基础肺容积和 1 秒用力呼气量（FEV1）/用力肺活量（FVC）和 FEV/预测值（pred）%。分析 HIF-1α 和 VEGF 基因的基因型和等位基因分布。使用 Kaplan-Meier 曲线和逻辑回归模型分析生存和 COPD 危险因素。分析 HIF-1α rs11549465 和 rs11549467 的单体型。病例组的 FEV/FVC 和 FEV1/pred%均低于对照组。病例组 HIF-1α rs11549465 CT+TT 基因型和 T 等位基因，以及 rs11549467 GA+AA 基因型和 A 等位基因的频率高于对照组。与 CC 基因型相比，rs11549465 CT+TT 基因型患者 COPD 发病风险更高。与 GG 基因型相比，rs11549467 GA+AA 基因型患者 COPD 发病风险更高，FEV/FVC 和 FEV1/pred%更低。与 CG 单体型相比，HIF-1α TA 单体型患者 COPD 发病风险更高。HIF-1α rs11549467 GG 基因型患者的生存率高于 GA+AA 基因型患者。HIF-1α rs11549467 多态性可能与 COPD 发病风险相关。
