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Association Of The Polymorphism Of Angiotensinogen With White Matter Lesions

Posted on:2017-02-14Degree:MasterType:Thesis
Country:ChinaCandidate:L W SunFull Text:PDF
GTID:2284330503992208Subject:Neurology
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Objectives To study the relationship between polymorphisms of angiotensinogen AGT(M235T)gene and white matter lesions(WMLs).Methods 241 WMLs cases and 104 normal brain MRI control cases were included prospectively. The following clinical data: gender, age, hypertention(with or without), diabetes mellitus(with or without), coronary atherosclerotic heart disease(with or without), smoking history, drinking history, level of education, carotid artery plaques, TC, HDL, LDL, UA, Hcy, FA, Vit B12 were gathered. The M235 T polymorphisms of AGT gene were determined by polymerase chain reaction(PCR)-restriction fragment length polymorphism(RFLP)technique and Sequenom system test. Gene counting method was used to calculate genotype frequency in both groups. The Montreal Cognitive Assessment scale(Mo CA) was administered to evaluate cognitive function of the two groups. According to the results, cases are divided into two subgroups(WMLs cognitive impairment and WMLs cognitively normal subgroups). Fazekas visual ratings were administered to evaluate white matter lesions of those subgroups. Statistical analysis: 1 WMLs was treated as dependent variable, and various clinical indicators as independent variables, using unconditional univariate and multivariate logistic regression,and analyze the AGT gene mutations are independent risk factors for cerebral white matter disease. 2 The chi-square test analysis of two groups of AGT gene polymorphism rate is to analysis whether AGT gene polymorphism is associated with cerebral white matter. 3 Analysising the risk factors of cognitive dysfunction in patients with white matter lisions.Results 1 The analysis of the clinical data of the two groups showed that the age(t=-7.194, P=0.000), hypertension incidence(χ2=11.984, P=0.001)of WMLs group ware significantly higher than those of control group,(P<0.05). 2 χ2test for AGT gene polymorphism ratio of the two groups showed: WMLs group of AGT gene MT genotype frequency(32% to 19.2%, χ2=7.519, P=0.022) and T allele frequency(21% to 12.5%, χ2=7.519, P=0.006) were significantly higher than those of control group, P<0.05. 3 Orderly classification multiple Logistic regression results show that elder 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), genetic mutation of T(OR=0.519, 95%CI: 0.289~0.933, P=0.028) are the risk factors for white matter lesions. 4 Compared the two subgroups, Fazekas scores of Cognitive impairment subgroup is significantly higher than cognitive normal subgroup(Z=9.379, P=9.379), P<0.05; The age of cognitive impairment subgroup is significantly higher than cognitively normal subgroup(t=5.211, P=5.211). The level of education of Cognitive impairment subgroup is significantly lower than cognitively normal subgroup(t=8.447, P=0.000). Between the two groups in gender(χ2=0.335, P=0.563), history of hypertension(t=1.139, P=0.286), coronary heart disease(t=1.124,P=0.289), diabetes(t=2.767,P=0.096), hyperlipidemia(t=1.235, P=0.266), carotid plaques(t=2.233, P=0.153), smoking(t=1.698, P=0.193), drinking(t=1.029, P=0.310), the difference was no statistically significant, P > 0.05. 5 Orderly classification multiple Logistic regression results show that elder age(OR=1.066, 95%CI=1.016~1.119, P=0.009), higher Fazekas scores( OR=6.796, 95%CI=3.555~12.991, P=0.009), lower level of education(OR=0.701, 95%CI=0.613~0.801, P=0.000) are risk factors for cognitive impairment in patients with WMLs.Conclusions 1 AGT MT genotype and T allele may be associated with the onset of cerebral white matter lesions. 2 AGT gene mutation(M235T) is one of the risk factors of white matter lesions. 3 Older age, lower education levels, higher Fazekas scores(severer white matter lesion) are risk factors for cognitive dysfunction in patients with WMLs.
Keywords/Search Tags:white matter lesions, gene polymorphism, angiotensinogen, celebral small vessel disease
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