【摘要】：目的探討腎素血管緊張素原(AGT)M235T基因多態(tài)性與腦白質(zhì)疏松癥(WMLs)的相關(guān)性。方法前瞻性納入241例經(jīng)頭顱MRI確診的腦白質(zhì)疏松癥患者為病例組和104例頭顱MRI正常者為對照組。收集所有研究對象臨床資料:年齡、性別、高血壓病史、糖尿病病史、高脂血癥病史、冠狀動脈粥樣硬化病史、吸煙史、飲酒史、受教育年限、是否伴頸動脈斑塊形成及血清總膽固醇、高密度脂蛋白、低密度脂蛋白、尿酸、同型半胱氨酸、葉酸、維生素B12等。采用聚合酶鏈反應(yīng)及聚合酶鏈反應(yīng)-限制片段長度多態(tài)性(RCR-RFLP)及Sequenom系統(tǒng)檢測兩組的AGT M235T基因多態(tài)性,對兩組各基因型及等位基因頻率用基因計數(shù)法進行計算。采用蒙特利爾認(rèn)知評估量表(Mo CA量表)評估WMLs組認(rèn)知功能,根據(jù)結(jié)果分為WMLs認(rèn)知損害亞組及WMLs認(rèn)知正常亞組,并進行Fazekas評分。統(tǒng)計分析:1以是否伴WMLs為因變量,以各觀察指標(biāo)為自變量,先行自變量的Logistic單因素回歸分析,對單因素分析中有統(tǒng)計學(xué)意義的自變量再行Logistic多因素回歸分析,2采用卡方檢驗分析兩組AGT基因多態(tài)性發(fā)生率是否有統(tǒng)計學(xué)差異,分析AGT基因多態(tài)性是否與WMLs相關(guān),3分析腦白質(zhì)疏松癥患者認(rèn)知功能障礙的危險因素。結(jié)果1兩組的各臨床資料分析結(jié)果顯示:腦白質(zhì)疏松癥組的年齡(t=-7.194,P=0.000)、高血壓病發(fā)生率(χ2=11.984,P=0.001)顯著高于對照組,差異有統(tǒng)計學(xué)意義(P均0.05),2兩組AGT基因多態(tài)性結(jié)果顯示:WMLs組AGT基因MT基因型頻率(32%對19.2%,χ2=7.519,P=0.022)及T等位基因頻率(21%對12.5%,χ2=7.519,P=0.006)顯著高于對照組,均P0.05,差異有統(tǒng)計學(xué)意義,3有序多分類Logistic回歸校正后結(jié)果顯示:年齡(OR=1.093,95%CI:1.055~1.132,P=0.000)、高血壓病(OR=0.500,95%CI:0.297~0.842,P=0.009)、基因突變(OR=0.519,95%CI:0.289~0.933,P=0.028)是腦白質(zhì)疏松癥的危險因素,4 WMLs患者認(rèn)知兩亞組相比,認(rèn)知損害亞組的Fazekas評分顯著高于認(rèn)知正常亞組(Z=-9.379,P=0.000),P0.05,差異有統(tǒng)計學(xué)意義;認(rèn)知損害亞組的年齡顯著高于認(rèn)知正常亞組(t=-5.211,P=0.000);認(rèn)知損害亞組的受教育程度顯著低于認(rèn)知正常亞組(t=8.447,P=0.000),未發(fā)現(xiàn)兩組間在性別(χ2=0.335,P=0.563)、高血壓病史(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)、高脂血癥病史(t=1.235,P=0.266)、頸動脈斑塊(t=2.233,P=0.153)、吸煙(t=1.698,P=0.193)、飲酒(t=1.029,P=0.310)上差異有統(tǒng)計學(xué)意義,P均0.05。5 WMLs患者認(rèn)知兩亞組有序多分類Logistic回歸校正后結(jié)果顯示:高齡(OR=1.066,95%CI=1.016~1.119,P=0.009)、高Fazekas評分(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患者認(rèn)知功能損害的危險因素。結(jié)論1 AGT MT基因型和T等位基因可能與腦白質(zhì)疏松癥的發(fā)病相關(guān)。2 AGT基因突變是腦白質(zhì)疏松癥的危險因素之一。3高齡、受教育程度低、程度較重的白質(zhì)病變是腦白質(zhì)疏松癥患者認(rèn)知功能障礙的危險因素。
[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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