AP-1基因多态性与缺血性脑卒中及其中医证型的相关性研究

发布时间：2018-06-05 03:04

本文选题：激活蛋白-1 + 缺血性脑卒中　；参考：《广西中医药大学》2016年硕士论文

【摘要】：目的:本研究旨在探讨激活蛋白-1(Activator protein-1,AP-1)基因rs1323288,rs2760501多态性与缺血性脑卒中(Ischemic stroke,IS)及其中医证型中风痰瘀阻证、气虚血瘀证遗传易感性的相关性,以及与IS相关数量性状的关联。方法:本研究采用病例对照设计,病例组共纳入816例缺血性脑卒中患者,对照共纳入816名同期住院的非IS患者及体检中心健康体检者(样本主要来源于导师课题)。使用统一问卷采集研究对象相关信息,汞柱式血压计测量研究对象血压,采用HITACHI日立全自动生化分析仪对IS患者总胆固醇(Total cholesterol,TC)、甘油三酯(Triglyceride,TG)、高密度脂蛋白胆固醇(High density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(Low-density lipoprotein cholesterol,LDL-C)进行检测。运用Sequenom基因分型技术对AP-1基因单核苷酸多态性位点(Single Nucleotide Polymorphisms,SNPs)rs1323288和rs2760501进行基因分型检测。应用SPSS16.0 for windows软件和PLINK软件进行统计分析。结果:1、AP-1基因的rs1323288和rs2760501在对照组中的基因型分布均符合HWE平衡定律(均为P0.050)。2、AP-1基因多态性与IS遗传易感性的关联分析:在总样本人群中,AP-1基因的rs1323288,rs2760501多态性与缺血性脑卒中遗传易感性的关联均无统计学意义(均为P0.050);在不同性别人群中,均未发现AP-1基因rs1323288,rs2760501多态性与IS的遗传易感性显著关联(均为P0.050);3、AP-1基因多态性与IS相关数量性状分析:(1)在总样本人群中,AP-1基因rs1323288与IS患者的TG(加性模型p_(adj)=0.040),LDL(隐性模型p_(adj)=0.007)血清水平显著相关;rs2760501多态性与IS患者HDL(隐性模型p_(adj)=0.041)血清水平显著相关,关联有统计学意义。(2)在男性中,rs2760501多态性与IS患者的HDL(隐性模型p_(adj)=0.002)血清水平存在统计学关联;(3)在女性中,rs1323288多态性与患者的TG(加性模型p_(adj)==0.000,显性模型p_(adj)==0.000)、HDL(加性模型p_(adj)=0.042,隐性模型p_(adj)=0.008)、LDL(隐性模型p_(adj)==0.002)血清水平及SBP(加性模型p_(adj)==0.004,显性模型p_(adj)==0.004)、DBP(加性模型p_(adj)=0.010,显性模型p_(adj)=0.008)显著相关,关联有统计学意义。rs2760501多态性与患者的TC(显性模型p_(adj)=0.039)血清水平存在统计学关联;4、AP-1基因多态性与缺血性中风中医证型的关联分析:在总样本人群中,AP-1基因的rs1323288,rs2760501多态性与缺血性中风风痰瘀阻证、气虚血瘀证遗传易感性的关联均无统计学意义(均为P0.050);在不同性别人群中,AP-1基因rs1323288,rs2760501多态性与缺血性中风风痰瘀阻证、气虚血瘀证的遗传易感性关联均无统计学意义(均为P0.050);5、AP-1基因多态性与缺血性中风中医证型相关数量性状分析:(1)在气虚血瘀证患者总样本人群中,在隐形模型下,AP-1基因rs2760501多态性与患者HDL(p_(adj)=0.012)、LDL(p_(adj)=0.043)血清水平显著关联,关联有统计学意义。(2)在男性中,rs2760501多态性与缺血性中风气虚血瘀证患者的HDL(加性模型p_(adj)=0.008,隐性模型p_(adj)=0.000)、LDL(隐性模型p_(adj)=0.042)血清水平关联具有统计学意义;(3)在女性中,rs1323288多态性与缺血性中风风痰瘀阻证患者的TG(加性模型p_(adj)=0.001、显性模型p_(adj)=0.002)、HDL(隐性模型p_(adj)=0.049)血清水平关联具有统计学意义,与缺血性中风气虚血瘀证SBP(加性模型p_(adj)=0.007、显性模型p_(adj)=0.008)水平存在显著关联。结论:AP-1基因rs1323288,rs2760501多态性与IS遗传易感性无关,与中风风痰瘀阻证、气虚血瘀证遗传易感性亦无关。rs2760501多态性可能影响中风气虚血瘀证患者血脂水平;rs1323288多态性可能影响女性缺血性中风风痰瘀阻证患者的血脂水平和气虚血瘀证患者血压水平。
[Abstract]:Objective: the purpose of this study was to explore the correlation between the genetic susceptibility of Activator protein-1 (AP-1) gene rs1323288, rs2760501 polymorphism and ischemic stroke (Ischemic stroke, IS) and TCM syndrome type apoplexy phlegm stasis syndrome, Qi deficiency and blood stasis syndrome, and the correlation with IS related quantitative characters. Methods: a case control study was used in this study. A total of 816 patients with ischemic stroke were included in the case group. A total of 816 non IS patients and physical examination centers in the medical center were included in the same period (the sample was mainly from the tutor topic). A unified questionnaire was used to collect the relevant information of the subjects. The mercury column sphygmomanometer was used to measure the blood pressure of the study object, and the automatic biochemical analysis of the HITACHI Hitachi was used. The total cholesterol (Total cholesterol, TC), triglyceride (Triglyceride, TG), high density lipoprotein cholesterol (High density lipoprotein cholesterol, HDL-C), low density lipoprotein cholesterol (Low-density TC) were detected. Single Nucleotide Polymorphisms (SNPs) rs1323288 and rs2760501 were used for genotyping detection. The statistical analysis was carried out by SPSS16.0 for Windows software and PLINK software. Results: 1, rs1323288 in AP-1 gene and the distribution of genotype distribution in the control group were all consistent with the law of equilibrium. The association analysis of genetic susceptibility: in the total sample population, the association of AP-1 gene rs1323288, rs2760501 polymorphism with the genetic susceptibility to ischemic stroke was not statistically significant (all P0.050); the AP-1 gene rs1323288 was not found in the different sex population, and the rs2760501 polymorphism was significantly associated with the genetic susceptibility of IS (all P0.050). 3, AP-1 gene polymorphism and IS related quantitative traits analysis: (1) in the total sample population, the AP-1 gene rs1323288 was significantly related to the serum level of TG (additive model p_ (adj) =0.040) in patients with IS and the serum level of LDL (recessive model p_ (adj)). (2) in male, there is a statistical correlation between rs2760501 polymorphism and the serum level of HDL (p_ (adj) =0.002) in IS patients; (3) in women, rs1323288 polymorphism and TG (additive model p_ (adj) ==0.000, dominant model p_). Adj) ==0.002) serum level and SBP (additive model p_ (adj) ==0.004, dominant model p_ (adj) ==0.004), DBP (additive model p_ (adj)), significant correlation, and statistically significant association with the serum level of patients. The correlation analysis of TCM syndrome type of ischemic stroke: in the total sample population, the association of AP-1 gene rs1323288, rs2760501 polymorphism and ischemic stroke wind phlegm stasis syndrome, Qi deficiency and blood stasis syndrome genetic susceptibility are not statistically significant (all P0.050); AP-1 gene rs1323288, rs2760501 polymorphism and ischemic apoplexy wind in different sex population The genetic susceptibility Association of qi deficiency syndrome, Qi deficiency and blood stasis syndrome has no statistical significance (all P0.050); 5, AP-1 gene polymorphism and TCM syndrome types of ischemic stroke are related quantitative characters analysis: (1) in the total sample population of patients with Qi deficiency and blood stasis syndrome, under the stealth model, the AP-1 gene rs2760501 polymorphism and the patient HDL (p_ (adj) =0.012), LDL (p_ (adj) =0.) 043) the serum level was significantly correlated, and the correlation was statistically significant. (2) in male, rs2760501 polymorphism and HDL (additive model p_ (adj) =0.008, recessive model p_ (adj) =0.000) and LDL (recessive p_ (adj) =0.042) blood clearing levels were statistically significant; (3) polymorphism and deficiency in women. The serum levels of TG (additive model p_ (adj) =0.001, dominant model p_ (adj) =0.002) and HDL (recessive model p_ (adj) =0.049) in patients with hemorrhagic stroke wind and phlegm stasis have statistical significance. There is a significant correlation with the level of ischemic stroke Qi deficiency and blood stasis syndrome (additive model = 0.007) and dominant model. 288, rs2760501 polymorphism is not related to the genetic susceptibility of IS, and the genetic susceptibility to Qi deficiency and blood stasis syndrome is not related to the stroke wind phlegm stasis syndrome, and the.Rs2760501 polymorphism may affect the blood lipid level of the patients with Qi deficiency and blood stasis syndrome, and the rs1323288 polymorphism may affect the blood lipid level of the patients with wind phlegm stasis syndrome and the blood stasis syndrome. Pressure level.
【学位授予单位】：广西中医药大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R277.7

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