脂联素基因多态性与汉族人群缺血性脑卒中关联分析
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摘要
研究背景
缺血性脑卒中是由非遗传因素、遗传因素共同作用的结果。目前非遗传影响因素研究大多数局限于一些特定因素与缺血性脑卒中的关联分析,故仍需系统分析缺血性脑卒中的非遗传影响因素,为缺血性脑卒中的预防提供依据。现阶段缺血性脑卒中遗传危险因素尚不明确,与之存在关联的基因及多态位点甚多；但有关脂联素基因多态性与缺血性脑卒中的关联研究很少,国内外罕见报道。
研究目的
明确汉族人群缺血性脑卒中的危险因素,探讨脂联素基因多态性与汉族人群缺血性脑卒中的关系,为缺血性脑卒中的预防提供依据。
研究方法
采用1：1配对的病例对照研究方案,收集深圳市两家大型综合性医院缺血性脑卒中首发病例,及按年龄相差≤5岁和性别、民族相同的匹配方式收集对照。使用统一的流行病学调查表对所有研究对象进行调查,用Taqman探针法检测脂联素基因多态性位点基因型。运用t检验、方差分析、趋势检验、卡方检验及单因素logistic回归分析影响因素与缺血性脑卒中的关系,并运用多因素logistic回归模型拟合在单因素分析存在统计差异的变量与缺血性脑卒中的关联。
研究结果
本研究共调查汉族缺血性脑卒中首发病例及对照各457例,其中男女性比为1.37：1,脑卒中病例平均年龄为61.75±9.98岁,对照平均年龄为61.24±10.06岁,年龄差异无统计学意义(P>0.05)。
将单因素分析存在统计差异的变量引入多因素logistic回归模型,高LDL(OR=2.85；95%CI：1.41,4.23)、向心性肥胖(OR=2.20；95%CI：1.38,3.25)、患有高血压(OR=7.62；95%CI：3.26,17.80)、在家庭经常感觉到压力(OR=3.13；95%CI：1.26,7.81)、吸烟(OR=2.09；95%CI：1.20,3.62)、高甘油三酯(OR=1.66；95%CI：1.10,2.49)、高血糖(OR=1.24；95%CI：1.03,1.49)为缺血性脑卒中独立危险因素,参加体育锻炼(OR=0.11；95%CI：0.02,0.51)、适度职业或退休活动(OR=0.28；95%CI：0.11,0.73)、进行午睡(OR=0.30；95%CI：0.13,0.71)、高HDL(OR=0.38；95%CI：0.15,0.93)、饮茶(OR=0.41；95%CI：0.18,0.94)、近两年食用植物油(OR=0.46；95%CI：0.31,0.69)、高频率食用其它蔬菜(OR=0.60；95%CI：0.44,0.83)以及高总蛋白浓度(OR=0.66；95%CI：0.50,0.88)为缺血性脑卒中的独立保护因素。
脂联素基因位点rs266729其等位基因C>G突变降低了缺血性脑卒中的易感性(OR=0.71；95%CI：0.55,0.93)；另一位点rs2241766其等位基因T>G纯合突变与汉族女性缺血性脑卒中易感性相关(P=0.04)。但把单因素分析存在统计学差异的所有变量进入多因素logistic回归分析模型,筛选缺血性脑卒中独立影响因素时,rs266729C>G突变差异不具有统计学意义(P=0.40)。
研究结论
中心性肥胖、高LDL、高甘油三酯、高血糖、高血压、吸烟仍是汉族人群缺血性脑卒中发生的主要危险因素,家庭压力、体育锻炼、体力活动等一些新的因素逐渐涌现并影响脑卒中发生。脂联素基因位点rs266729多态性与缺血性脑卒中存在显著负相关,但rs266729C>G突变不是缺血性脑卒中独立保护因素。
Background
Many risk factors contribute to the occurrence and development of ischemic stroke (IS), and all of the factors can be devided into non-genetic factors and genetic factors. Nowadays, there are many studies regarding the relationship and mechanisms between different non-genetic risk factors and IS. However, most of them are limited to the relations of some specific factors to IS. So it is necessary to analyze the non-genetic risk factors of IS systematically to prevent and control IS. At present, many genes and their polymorphisms are associated with IS, and the genetic risk factors of IS have not been conformed exactly. But few studies on the relationship between polymorphisms of adiponectin gene and IS are reported in the world.
Objective
The purpose of this study is to explore the risk factors of IS and the relationship between polymorphisms of adiponectin gene and IS in the Han Chinese population, and to prevent and control IS.
Methods
A 1:1 matched case-control study method was applied to investigate initial IS cases, The IS cases were selected from two large general hospitals of Shenzhen, and controls were matched to the cases with the same gender and ethnicity, and age differed within 5 years. All the cases and controls were interviewed by the same epidemiology questionnaire. Taqman probe of Fluorescence quantitative PCR was used to detect the genotype of adiponectin gene loci. T test, analysis of variance, trend test, chi-square test, and logistic regression were applied to analyze the data.
Results
457 initial cases and 457 controls were investigated and the male and female ratio is 1.37:1. There is no statistical difference between the age of cases and controls (P> 0.05), while the average age of cases is 61.75±9.98 years and that is 61.24±10.06 years in controls.
Those differential factors in univariate analysis are analyzed further by multivariate logistic regression and the results indicate that high level of LDL(OR=2.85; 95%CI: 1.41,4.23), central obesity(OR=2.20; 95%CI:1.38,3.25), hypertension(OR=7.62; 95%CI:3.26,17.80), family stress(OR=3.13; 95%CI:1.26,7.81), smoking(OR=2.09; 95%CI:1.20,3.62), high level of triglycerides(OR=1.66; 95%CI:1.10,2.49) and high levels of blood glucose(OR=1.24; 95%CI:1.03,1.49) were significant independent risk factors for IS. Whereas, the independent protective factors of IS were physical activity(OR=0.11; 95%CI:0.02,0.51), partial retirement or professional activity (OR=0.28; 95%CI:0.11,0.73), afternoon napping(OR=0.30; 95%CI:0.13,0.71), high level of HDL(OR=0.38; 95%CI:0.15,0.93), tea drinking(OR=0.41; 95%CI:0.18,0.94), consumption of vegetable oil in two recent years(OR=0.46; 95%CI: 0.31,0.69), high-frequency consumption of other vegetables(OR=0.60; 95%CI:0.44,0.83), and high level of total protein(OR=0.66; 95%CI:0.50,0.88).
C>G mutation of rs266729 of Adiponectin gene decreased the risk of IS in the Han Chinese population(OR=0.71; 95%CI: 0.55,0.93); and T>G homozygous mutation of rs2241766 was related to the susceptibility of Han Chinese women (P=0.04). However, C>G mutation of rs266729 were not statistically significant after the adjustment of the differential varables in Univariate analysis (P=0.40).
Conclusions
central obesity, high level of LDL, triglycerides, and blood glucose, hypertension and smoking remain to be the main risk factors of IS in Han Chinese population. Some noval risk factors have been emerging and changing the susceptibility of IS, such as family stress, physical exercise, and physical activity. The C>G mutation of rs266729 decreases the risk of IS, but it is not the independent protective factor of IS.
缺血性脑卒中是由非遗传因素、遗传因素共同作用的结果。目前非遗传影响因素研究大多数局限于一些特定因素与缺血性脑卒中的关联分析,故仍需系统分析缺血性脑卒中的非遗传影响因素,为缺血性脑卒中的预防提供依据。现阶段缺血性脑卒中遗传危险因素尚不明确,与之存在关联的基因及多态位点甚多；但有关脂联素基因多态性与缺血性脑卒中的关联研究很少,国内外罕见报道。
研究目的
明确汉族人群缺血性脑卒中的危险因素,探讨脂联素基因多态性与汉族人群缺血性脑卒中的关系,为缺血性脑卒中的预防提供依据。
研究方法
采用1：1配对的病例对照研究方案,收集深圳市两家大型综合性医院缺血性脑卒中首发病例,及按年龄相差≤5岁和性别、民族相同的匹配方式收集对照。使用统一的流行病学调查表对所有研究对象进行调查,用Taqman探针法检测脂联素基因多态性位点基因型。运用t检验、方差分析、趋势检验、卡方检验及单因素logistic回归分析影响因素与缺血性脑卒中的关系,并运用多因素logistic回归模型拟合在单因素分析存在统计差异的变量与缺血性脑卒中的关联。
研究结果
本研究共调查汉族缺血性脑卒中首发病例及对照各457例,其中男女性比为1.37：1,脑卒中病例平均年龄为61.75±9.98岁,对照平均年龄为61.24±10.06岁,年龄差异无统计学意义(P>0.05)。
将单因素分析存在统计差异的变量引入多因素logistic回归模型,高LDL(OR=2.85；95%CI：1.41,4.23)、向心性肥胖(OR=2.20；95%CI：1.38,3.25)、患有高血压(OR=7.62；95%CI：3.26,17.80)、在家庭经常感觉到压力(OR=3.13；95%CI：1.26,7.81)、吸烟(OR=2.09；95%CI：1.20,3.62)、高甘油三酯(OR=1.66；95%CI：1.10,2.49)、高血糖(OR=1.24；95%CI：1.03,1.49)为缺血性脑卒中独立危险因素,参加体育锻炼(OR=0.11；95%CI：0.02,0.51)、适度职业或退休活动(OR=0.28；95%CI：0.11,0.73)、进行午睡(OR=0.30；95%CI：0.13,0.71)、高HDL(OR=0.38；95%CI：0.15,0.93)、饮茶(OR=0.41；95%CI：0.18,0.94)、近两年食用植物油(OR=0.46；95%CI：0.31,0.69)、高频率食用其它蔬菜(OR=0.60；95%CI：0.44,0.83)以及高总蛋白浓度(OR=0.66；95%CI：0.50,0.88)为缺血性脑卒中的独立保护因素。
脂联素基因位点rs266729其等位基因C>G突变降低了缺血性脑卒中的易感性(OR=0.71；95%CI：0.55,0.93)；另一位点rs2241766其等位基因T>G纯合突变与汉族女性缺血性脑卒中易感性相关(P=0.04)。但把单因素分析存在统计学差异的所有变量进入多因素logistic回归分析模型,筛选缺血性脑卒中独立影响因素时,rs266729C>G突变差异不具有统计学意义(P=0.40)。
研究结论
中心性肥胖、高LDL、高甘油三酯、高血糖、高血压、吸烟仍是汉族人群缺血性脑卒中发生的主要危险因素,家庭压力、体育锻炼、体力活动等一些新的因素逐渐涌现并影响脑卒中发生。脂联素基因位点rs266729多态性与缺血性脑卒中存在显著负相关,但rs266729C>G突变不是缺血性脑卒中独立保护因素。
Background
Many risk factors contribute to the occurrence and development of ischemic stroke (IS), and all of the factors can be devided into non-genetic factors and genetic factors. Nowadays, there are many studies regarding the relationship and mechanisms between different non-genetic risk factors and IS. However, most of them are limited to the relations of some specific factors to IS. So it is necessary to analyze the non-genetic risk factors of IS systematically to prevent and control IS. At present, many genes and their polymorphisms are associated with IS, and the genetic risk factors of IS have not been conformed exactly. But few studies on the relationship between polymorphisms of adiponectin gene and IS are reported in the world.
Objective
The purpose of this study is to explore the risk factors of IS and the relationship between polymorphisms of adiponectin gene and IS in the Han Chinese population, and to prevent and control IS.
Methods
A 1:1 matched case-control study method was applied to investigate initial IS cases, The IS cases were selected from two large general hospitals of Shenzhen, and controls were matched to the cases with the same gender and ethnicity, and age differed within 5 years. All the cases and controls were interviewed by the same epidemiology questionnaire. Taqman probe of Fluorescence quantitative PCR was used to detect the genotype of adiponectin gene loci. T test, analysis of variance, trend test, chi-square test, and logistic regression were applied to analyze the data.
Results
457 initial cases and 457 controls were investigated and the male and female ratio is 1.37:1. There is no statistical difference between the age of cases and controls (P> 0.05), while the average age of cases is 61.75±9.98 years and that is 61.24±10.06 years in controls.
Those differential factors in univariate analysis are analyzed further by multivariate logistic regression and the results indicate that high level of LDL(OR=2.85; 95%CI: 1.41,4.23), central obesity(OR=2.20; 95%CI:1.38,3.25), hypertension(OR=7.62; 95%CI:3.26,17.80), family stress(OR=3.13; 95%CI:1.26,7.81), smoking(OR=2.09; 95%CI:1.20,3.62), high level of triglycerides(OR=1.66; 95%CI:1.10,2.49) and high levels of blood glucose(OR=1.24; 95%CI:1.03,1.49) were significant independent risk factors for IS. Whereas, the independent protective factors of IS were physical activity(OR=0.11; 95%CI:0.02,0.51), partial retirement or professional activity (OR=0.28; 95%CI:0.11,0.73), afternoon napping(OR=0.30; 95%CI:0.13,0.71), high level of HDL(OR=0.38; 95%CI:0.15,0.93), tea drinking(OR=0.41; 95%CI:0.18,0.94), consumption of vegetable oil in two recent years(OR=0.46; 95%CI: 0.31,0.69), high-frequency consumption of other vegetables(OR=0.60; 95%CI:0.44,0.83), and high level of total protein(OR=0.66; 95%CI:0.50,0.88).
C>G mutation of rs266729 of Adiponectin gene decreased the risk of IS in the Han Chinese population(OR=0.71; 95%CI: 0.55,0.93); and T>G homozygous mutation of rs2241766 was related to the susceptibility of Han Chinese women (P=0.04). However, C>G mutation of rs266729 were not statistically significant after the adjustment of the differential varables in Univariate analysis (P=0.40).
Conclusions
central obesity, high level of LDL, triglycerides, and blood glucose, hypertension and smoking remain to be the main risk factors of IS in Han Chinese population. Some noval risk factors have been emerging and changing the susceptibility of IS, such as family stress, physical exercise, and physical activity. The C>G mutation of rs266729 decreases the risk of IS, but it is not the independent protective factor of IS.
引文
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