高原低氧环境与平原地区常住居民HIF⁃1、VEGF水平及与阿尔茨海默病易感性的相关性和交互作用

Correlation and Interaction between HIF-1 and VEGF Expression Levels and Susceptibility to Alzheimer's Disease in Permanent Residents in Plateau Hypoxic Environment and Plain Area

目的分析高原低氧环境与平原地区常住居民缺氧诱导因子-1(HIF-1)、血管内皮生长因子(VEGF)的水平差异及与阿尔茨海默病(AD)易感性的相关性和交互作用。方法选取2020年1月—2023年1月高原低氧环境地区180例常住居民和平原地区180例常住居民作为研究对象,根据是否患有AD分为AD组、无AD组,比较高原低氧环境地区和平原地区2组HIF-1、VEGF水平差异,采用多因素Logistic回归分析AD易感性的相关影响因素,采用相对危险度分析不同HIF-1、VEGF水平患者罹患AD的风险,采用交互作用系数γ和比值比(OR)分析HIF-1、VEGF水平对AD易感性的交互作用及其作用类型。结果高原低氧环境、平原地区AD组HIF-1水平高于无AD组,VEGF水平低于无AD组(P<0.01);高原低氧环境地区AD组、无AD组HIF-1水平高于平原地区对应AD组、无AD组,VEGF水平低于平原地区对应AD组、无AD组(P<0.05)。多因素Logistic回归分析显示,HIF-1、VEGF水平与高原低氧环境地区、平原地区及总体AD易感性显著相关(P<0.05,P<0.01)。HIF-1高水平患者罹患AD危险度是低水平患者的6.174倍,VEGF高水平患者罹患AD危险度是低水平患者的0.327倍(P<0.01)。单独HIF-1水平升高所致的OR为6.200,单独VEGF水平降低所致的OR为10.075,二者共存时所致OR为21.097,符合次相乘交互作用模型。结论HIF-1水平升高、VEGF水平降低与AD易感性密切相关;高原低氧环境可导致HIF-1水平进一步升高,VEGF水平进一步降低,增加罹患AD的危险度;HIF-1水平升高、VEGF水平降低对AD易感性产生了正向交互作用,并符合次相乘交互作用模型。

Objective To analyze the difference in expression of hypoxia induced-factor 1(HIF-1)and vascular endothelial growth factor(VEGF)in permanent residents in plateau hypoxia environment and plain area,and the their correlation and interaction with the susceptibility of Alzheimer's disease(AD).Methods From January 2020 to January 2023,180 permanent residents in plateau hypoxic environment and 180 permanent residents in plain area were selected as research subjects.They were divided into AD group and non-AD group according to presence of AD.The differences in HIF-1 and VEGF levels between the two groups in plateau hypoxic environment and plain area were compared.Multiple Logistic regression analysis was used to analyze the related influencing factors of AD susceptibility.Relative risk(RR)was used to analyze the risk of AD in patients with different HIF-1 and VEGF levels,and interaction coefficientγand odds ratio(OR)were used to analyze the interaction of HIF-1 and VEGF levels with AD susceptibility as well as the types of action.Results HIF-1 level in AD group was higher than that in non-AD group,while VEGF level was lower than that in non-AD group in plateau hypoxic environment and plain area(P<0.01).HIF-1 level in AD group and non-AD group in plateau hypoxic environment was higher than that in AD group and no AD group in plain area,while VEGF level was lower than that in AD group and non-AD group in plain area(P<0.05).Multivariate Logistic regression analysis showed that HIF-1 and VEGF levels were significantly correlated with plateau hypoxic environment,plain area and the overall AD susceptibility(P<0.05,P<0.01).The risk of AD in patients with high levels of HIF-1 was 6.174 times higher than that in patients with low levels,and the risk of AD in patients with high levels of VEGF was 0.327 times higher than that in patients with low levels(P<0.01).The OR caused by the increase of HIF-1 level alone was 6.200,by the decrease of VEGF level alone was 10.075,and by the coexistence of the two was 21.097,which was consistent with the sub-multiplication model.Conclusion Increased HIF-1 level and decreased VEGF level are closely related to AD susceptibility.Plateau hypoxic environment can further increase the level of HIF-1,decrease the level of VEGF,and increase the risk of AD.Increased HIF-1 level and decreased VEGF level had a positive interaction effect on AD susceptibility,which was consistent with the sub-multiplication interaction model.