血管内皮生长因子基因－2578 C >A多态性与中国山东地区汉族人群颈动脉粥样硬化的相关性

目的：探讨血管内皮生长因子（vascular endothelial growth factor,VEGF）基因－2578 C＞A多态性与中国山东地区汉族人群颈动脉粥样硬化的关系。方法纳入年龄在45~85岁之间的山东地区汉族受试者384例，根据颈部血管超声检查结果分为内膜－中膜厚度（ intim a-m edia thickness, IMT ）增厚组（248例）和对照组（136例）。收集2组人口统计学资料、血管危险因素和血液生化指标等基线临床资料，应用聚合酶链反应检测VEGF 基因－2578C＞A多态性基因型和等位基因，采用多变量logistic回归分析确定颈动脉IMT 增厚的独立危险因素。结果 IMT 增厚组高血压（70.6％对59.6％；χ2=4.793，P=0.032）、糖尿病（18.4％对29.0％；χ2=5.281，P=0.027）、高脂血症（45.2％对33.1％；χ2=7.883， P=0.006）、既往卒中或短暂性脑缺血发作史（29.0％对16.9％；χ2=6.294，P=0.009）、吸烟（35.9％对19.9％；χ2=10.708，P=0.001）的构成比以及总胆固醇（4.82±1.25）mmol/L对（4.57±0.94）mmol/L；t=－2.072，P=0.039]、三酰甘油（中位数，四分位数间距）1.71（0.84~2.22）mmol/L对1.53（1.08~2.59）mmol/L；Z=－2.560，P=0.010]、低密度脂蛋白胆固醇（2.86±1.01）mmol/L对（2.64±0.85）mmol/L；t=－2.407，P=0.033]和高密度脂蛋白胆固醇（1.58±0.72）mmol/L对（1.43±0.46）mmol/L；t=－2.183，P=0.030]与对照组差异有统计学意义。2组间基因型分布频率差异有统计学意义（χ2=10.131；P=0.006），IMT增厚组C等位基因频率与对照组差异有统计学意义（78.2％对70.2％；χ2=6.068，P=0.014）。多变量logistic回归分析显示，CC基因型（优势比1.132，95％可信区间1.021~2.141；P=0.029）是颈动脉IMT 增厚的独立危险因素。在248例IMT 增厚患者中，213例患者至少存在1个斑块，其中斑块指数1~276例（39.6％），3~4107例（43.15％），5~830例（12.1％）。不同斑块指数组基因型（χ2=6.766，P=0.149）和等位基因（χ2=0.185，P=0.667）分布频率差异无统计学意义。结论在中国山东汉族人群中，VEGF基因启动子区－2578单核苷酸多态性与颈动脉粥样硬化相关，C等位基因可能是其遗传易感因素。

Correlation betw een -2578C > A polymorphism of vascular endothelium grow th factor gene and carotid atherosclerosis in Chinese Han population in Shandong,China

ObjectiveToinvestigatethecorrelationbetween-2578C>Apolymorphismofvascular endothelium grow th factor (VEGF) gene and carotid atherosclerosis in Chinese Han population in Shandong, China. Methods A total of 384 subjects aged 45-85 in Chinese Han population in Shandong, China w ere enroled. They were divided into either an increased intima-media thickness (IMT) group ( n=248) or a control group (n=136) according to the vascular ultrasound results. The baseline clinical data, such as the demographic data, vascular risk factors, and blood biochemical indicators in both groups were colected. Polymerase chain reaction w as used to detect the VEGF gene -2578C>A polymorphism genotype and alele. Multivariate logistic regression analysis was used to identify the independent risk factors for increased carotid IMT. Results The proportions of hypertension ( 70.6%vs.59.6%;χ2 =4.793, P=0.032), diabetes (18.4%vs.29.0%; χ2 =5.281, P=0.027), hyperlipidemia ( 45.2%vs.33.1%; χ2 =7.883, P=0.006), previous previous stroke or transient ischemic attack (29.0%vs.16.9%;χ2 =6.294, P=0.009), smoking (35.9%vs.19.9%;χ2 =10.708, P=0.001), as w el as total cholesterol ( 4.82 ±1.25 mmol/L vs.4.57 ± 0.94 mmol/L; t= -2.072, P= 0.039 ), triglyceride ( median, interquartile range; 1.710.84-2.22] mmol/L vs.1.531.08-2.59] mmol/L;Z= -2.560 P=0.010), low-density lipoprotein cholesterol (2.86 ±1.01 mmol/L vs.2.64 ±0.85 mmol/L; t= -2.407, P= 0.033 ), and high-density lipoprotein cholesterol (1.58 ±0.72 mmol/L vs.1.43 ±0.46 mmol/L;t= -2.183, P=0.030) in the increased IMT group, and there w ere significant differences compared w ith the control group. There w as significant difference in genotype frequency betw een the 2 groups (χ2 =10.131; P=0.006). There w as significant difference in C alele frequency between the increased IMT group and the control group (78.2% vs. 70.2%;χ2 =6.068, P=0.014). Multivariate logistic regression analysis showed that CC genotype (odds ratio 1.132, 95%confidence interval 1.021-2.141;P=0.029) w as an independent risk factor for increased carotid IMT. In 248 patients w ith increased IMT, 213 had at least 1 plaque, 76 (39.6%) of them w ere 1-2, 107 (43.15%) w ere 3-4, and 30 (12.1%) w ere 5-8 in plaque index. There w ere no significant differences in frequencies of genotypes (χ2 =6.766, P=0.149) and alele (χ2 =0.185, P=0.667) in the different plaque index groups. Conclusions -2578 single nucleotide polymorphism in the VEGF gene promoter is associated w ith carotid atherosclerosis, and C al ele may be its genetic susceptibility factor in Chinese Han population in Shandong, China.