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缺氧诱导因子-1α和血管内皮生长因子的遗传多态性与慢性阻塞性肺疾病风险增加的关联:一项病例对照研究。

The association of genetic polymorphisms of hypoxia inducible factor-1 alpha and vascular endothelial growth factor with increased risk of chronic obstructive pulmonary disease: A case-control study.

机构信息

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.

出版信息

Kaohsiung J Med Sci. 2017 Sep;33(9):433-441. doi: 10.1016/j.kjms.2017.05.014. Epub 2017 Jul 5.

Abstract

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.

摘要

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。

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