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脑白质疏松症患者血管紧张素原基因多态性的研究

发布时间:2018-10-18 10:41
【摘要】:目的探讨肾素血管紧张素原(AGT)M235T基因多态性与脑白质疏松症(WMLs)的相关性。方法前瞻性纳入241例经头颅MRI确诊的脑白质疏松症患者为病例组和104例头颅MRI正常者为对照组。收集所有研究对象临床资料:年龄、性别、高血压病史、糖尿病病史、高脂血症病史、冠状动脉粥样硬化病史、吸烟史、饮酒史、受教育年限、是否伴颈动脉斑块形成及血清总胆固醇、高密度脂蛋白、低密度脂蛋白、尿酸、同型半胱氨酸、叶酸、维生素B12等。采用聚合酶链反应及聚合酶链反应-限制片段长度多态性(RCR-RFLP)及Sequenom系统检测两组的AGT M235T基因多态性,对两组各基因型及等位基因频率用基因计数法进行计算。采用蒙特利尔认知评估量表(Mo CA量表)评估WMLs组认知功能,根据结果分为WMLs认知损害亚组及WMLs认知正常亚组,并进行Fazekas评分。统计分析:1以是否伴WMLs为因变量,以各观察指标为自变量,先行自变量的Logistic单因素回归分析,对单因素分析中有统计学意义的自变量再行Logistic多因素回归分析,2采用卡方检验分析两组AGT基因多态性发生率是否有统计学差异,分析AGT基因多态性是否与WMLs相关,3分析脑白质疏松症患者认知功能障碍的危险因素。结果1两组的各临床资料分析结果显示:脑白质疏松症组的年龄(t=-7.194,P=0.000)、高血压病发生率(χ2=11.984,P=0.001)显著高于对照组,差异有统计学意义(P均0.05),2两组AGT基因多态性结果显示:WMLs组AGT基因MT基因型频率(32%对19.2%,χ2=7.519,P=0.022)及T等位基因频率(21%对12.5%,χ2=7.519,P=0.006)显著高于对照组,均P0.05,差异有统计学意义,3有序多分类Logistic回归校正后结果显示:年龄(OR=1.093,95%CI:1.055~1.132,P=0.000)、高血压病(OR=0.500,95%CI:0.297~0.842,P=0.009)、基因突变(OR=0.519,95%CI:0.289~0.933,P=0.028)是脑白质疏松症的危险因素,4 WMLs患者认知两亚组相比,认知损害亚组的Fazekas评分显著高于认知正常亚组(Z=-9.379,P=0.000),P0.05,差异有统计学意义;认知损害亚组的年龄显著高于认知正常亚组(t=-5.211,P=0.000);认知损害亚组的受教育程度显著低于认知正常亚组(t=8.447,P=0.000),未发现两组间在性别(χ2=0.335,P=0.563)、高血压病史(t=1.139,P=0.286)、冠心病病史(t=1.124,P=0.289)、糖尿病病史(t=2.767,P=0.096)、高脂血症病史(t=1.235,P=0.266)、颈动脉斑块(t=2.233,P=0.153)、吸烟(t=1.698,P=0.193)、饮酒(t=1.029,P=0.310)上差异有统计学意义,P均0.05。5 WMLs患者认知两亚组有序多分类Logistic回归校正后结果显示:高龄(OR=1.066,95%CI=1.016~1.119,P=0.009)、高Fazekas评分(OR=6.796,95%CI=3.555~12.991,P=0.009)、低教育程度(OR=0.701,95%CI=0.613~0.801,P=0.000)是WMLs患者认知功能损害的危险因素。结论1 AGT MT基因型和T等位基因可能与脑白质疏松症的发病相关。2 AGT基因突变是脑白质疏松症的危险因素之一。3高龄、受教育程度低、程度较重的白质病变是脑白质疏松症患者认知功能障碍的危险因素。
[Abstract]:Objective to investigate the association of renin angiotensinogen (AGT) M235T gene polymorphism with leukoaraiosis (WMLs). Methods 241 cases of leukoaraiosis diagnosed by MRI and 104 cases of normal head MRI were included as control group. Clinical data of all subjects were collected: age, sex, history of hypertension, history of diabetes, history of hyperlipidemia, history of coronary atherosclerosis, history of smoking, history of alcohol consumption, length of education. With carotid plaque formation and serum total cholesterol, high density lipoprotein, low density lipoprotein, uric acid, homocysteine, folic acid, vitamin B12 and so on. Polymerase chain reaction (PCR), polymerase chain reaction-restriction fragment length polymorphism (RCR-RFLP) and Sequenom system were used to detect the polymorphism of AGT M235T gene in the two groups. The genotypes and allelic frequencies of the two groups were calculated by gene counting method. The cognitive function of WMLs group was assessed by Montreal Cognitive Assessment scale (Mo CA). According to the results, they were divided into WMLs cognitive impairment subgroup and WMLs cognitive normal subgroup, and Fazekas scores were performed. Statistical analysis: (1) Logistic single factor regression analysis of independent variables with or without WMLs as dependent variable, with each observation index as independent variable; Logistic multivariate regression analysis was performed for independent variables with statistical significance in univariate analysis. (2) chi-square test was used to analyze whether there was statistical difference in the incidence of AGT gene polymorphism between the two groups. To analyze whether AGT gene polymorphism is associated with WMLs, and to analyze the risk factors of cognitive dysfunction in patients with leukoaraiosis. Results (1) the clinical data of the two groups showed that the age and the incidence of hypertension in the leukoaraiosis group were significantly higher than those in the control group (蠂 ~ 2 / 7.194 / P ~ (0.000), 蠂 ~ (2 / 2) = 11.984 / P ~ (0.001), respectively. The frequency of MT genotype of AGT gene (32% vs 19.2%) and the frequency of T allele (21% vs 12.5) in WMLs group were significantly higher than those in control group. The results of Logistic regression showed that age (OR=1.093,95%CI:1.055~1.132,P=0.000), hypertension (OR=0.500,95%CI:0.297~0.842,P=0.009) and gene mutation (OR=0.519,95%CI:0.289~0.933,P=0.028) were risk factors of leukoaraiosis. The Fazekas score in the cognitive impairment subgroup was significantly higher than that in the normal cognitive subgroup (ZP0. 379P0. 000), and the difference was statistically significant (P0. 05). The age of the cognitive impairment subgroup was significantly higher than that of the normal cognitive subgroup (t = 5.211P = 0.000), the educational level of the cognitive impairment subgroup was significantly lower than that of the cognitive normal subgroup (t = 8.447, P = 0.000). There was no gender (蠂 ~ 2 / 0.335P ~ (0.563), a history of hypertension (t 1.139p _ (0.286), a history of coronary heart disease (t = 1.124P _ (0.289), a history of diabetes mellitus (n = 0.289). (t=2.767,P=0.096),楂樿剛琛,

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