【作者】 尹晶；

【导师】 李震中； 张国华；

【作者基本信息】 河北医科大学 ， 神经病学， 2007， 硕士

【摘要】 目的:国内外大量研究表明,脂蛋白脂酶(LPL)不同位点的基因多态性对血脂水平(尤为甘油三酯,TG)有一定影响,而高甘油三酯血症(Hypertriglyceridaemia,HTG)又是动脉粥样硬化性脑梗死(atherosclerotic cerebral infarction,ACI)的重要危险因素。本研究主要探讨中国河北汉族人群LPL基因PvuⅡ及N291S单核苷酸多态性与高甘油三酯血症及动脉粥样硬化性脑梗死的关系。方法:对41例动脉粥样硬化性脑梗死患者和88例人群随机挑选对照进行病例对照研究。运用多聚酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)分析技术分别检测LPL基因PvuⅡ及N291S多态性,并测定血清TG含量。分析高血压、糖尿病、高血脂、吸烟、体重指数及LPL基因PvuⅡ及N291S多态性位点与ACI发病的相关性。结果1 ACI组与对照组的一般情况:两组人群的年龄和性别比例没有统计学差异。ACI组的BMI高于对照组,但无统计学意义(P>0.05),有吸烟史、糖尿病史和高血压病史者明显多于对照组(P<0.05)。2两组中PvuⅡ位点基因型均以P+P-型多见,其次为P+P+型,而P-P-型比较少见;其等位基因频率分布均以P+等位基因为常见等位基因,P-等位基因为少见等位基因。两组人群中PvuⅡ多态性基因型分布符合Hardy-Weinberg平衡,具有群体代表性。ACI组和对照组P+P+、P+P-、P-P-基因型频率分别为0.341vs0.295、0.512vs0.534、0.147vs0.171,差异无统计学意义(P>0.05);两组P+、P-等位基因频率分别为0.598 vs0.563、0.402vs0.437,差异亦无统计学意义(P>0.05)。3 ACI组中P+P+、P+P-、P-P-基因型的血清TG水平逐渐递减(3.50±2.32vs2.75±2.07vs1.88±1.04),但无统计学差异(F=1.44,P=0.2504);对照组中P+P+、P+P-、P-P-基因型的血清TG水平分别为(2.07±0.61vs1.88±0.57vs1.87±0.57),三者比较差异亦无统计学意义(F=1.01,P=0.3672)。4 ACI组中HTG、NTG亚组P+P+型、P+P-型、P-P-型频率分别为37.0%vs28.6%、55.6%vs42.9%、7.4%vs28.5%,两亚组比较无统计学差异(X2=0.038,P =0.846>0.05),P+、P-等位基因频率分别为64.8%vs50.0%、35.2%vs50.0%,差异亦无统计学意义(P>0.05);对照组中HTG、NTG亚组P+P+型、P+P-型、P-P-型频率分别为22.4%vs38.5%、57.1%vs48.7%、11.5%vs12.8%,两亚组比较无统计学差异(X2=2.907,P = 0.234>0.05),P+、P-等位基因频率分别为51.0%vs62.8%、49.0%vs37.2%,差异亦无统计学意义(P>0.05)。5以是否患ACI为应变量,高血压、糖尿病、吸烟、携带P+等位基因、肥胖(BMI)等ACI常见危险因素为自变量,进行多因素Logistic回归分析,以a =0.1为入选和排除标准,结果发现吸烟史(OR=3.367)、高血压病史(OR=3.185)、糖尿病病史(OR=3.409)进入模型,是ACI的独立危险因素;而携带P+等位基因则未进入模型,不是ACI的独立危险因素。6 N291S突变在病对两组中均未发现。结论1 LPL基因P+等位基因与血清TG水平无明显相关性。2 LPL基因P+等位基因与ACI发生不相关,可能不足以构成ACI的独立遗传性危险因子。3 LPL基因N291S突变在病对两组中均未发现,推测在欧洲白种人存在的与HTG、ACI的发生相关联的LPL常见基因变异N291S可能与中国人HTG、ACI的发生无关。4吸烟史、高血压史、糖尿病史是ACI的独立危险因素,与以往认识相符。5本组实验未发现肥胖与ACI发生存在直接相关性。更多还原

【Abstract】 Objective: Many Researches show that, different gene polymorphisms of Lipoprotein lipase(LPL) have certain effects on blood lipids (especially on triglyceride , TG), while hypertriglyceridemia(HTG) is an important risk factor for atherosclerotic cerebral infarction(ACI). The aim of this study is to investigate the association of PvuⅡand N291S polymorphisms in LPL gene with HTG and ACI.Methods: The genotype and allele frequencies of LPL gene polymorphisms (PvuⅡand N291S) were analyzed by PCR-restriction fragment length polymorphism in 41 ACI patients and 88 random-selected healthy control individuals. Meanwhile serum triglyceride levels were determined. The correlation of high blood pressure, diabetes, high cholesterol, smoking, body mass index, PvuⅡand N291S gene polymorphisms with the incidence of ACI were also analyzed.Results1 The general state of ACI group and the control group: In two groups there was no difference between the age and sex ratio. ACI group of patients have higher body mass index without statistical significance (P>0.05), but Significantly higher smoking rates, prevalence of hypertension and diabetes compared with the control group (P<0.05).2 In the two groups, P+P- genotype were prevalent, followed by P+P+ and P-P- is relatively rare; P+ is the main allele and P- is the rare allele. The genotype distribution of PvuⅡin both groups corresponds to Hardy-Weinberg equilibrium, with groups’representation. In ACI group and the control group, P+P+、P+P-、P-P- genotype frequencies are 0.341vs0.295, 0.512vs0.534, 0.147vs0.171 respectively, without statistical significance (P>0.05); P+、P- allele frequencies are 0.598vs0.563, 0.402vs0.437 respectively, the differences between the two groups were also without statistically significant (P>0.05).3 In ACI group, serum triglyceride concentrations of P+P+、P+P-、P-P- genotype are 3.50±2.32vs2.75±2.07vs1.88±1.04 respectively, exhibiting a gradual decrease, but without statistical significance(F=1.44,P=0.2504). In control group, serum triglyceride concentrations of P+P+、P+P-、P-P- genotype are 2.07±0.61vs1.88±0.57vs1.87±0.57 respectively, also without statistically significant differences among the three(F=1.01,P= 0.3672).4 In HTG and NTG subgroups of ACI group, P+P+、P+P-、P-P- genotype frequencies are 0.370vs0.286, 0.556vs0.429, 0.074vs0.285 respectively, without statistical significance (X2= 0.038,P= 0.846>0.05). P+、P- allele frequencies are 0.648vs 0.500, 0.352vs0.500 respectively, without statistical significance (P>0.05). In HTG and NTG subgroups of the controls, P+P+、P+P-、P-P- genotype frequencies are 0.224vs0.385, 0.571vs 0.487, 0.115vs0.128 respectively, without statistical significance (X2=2.907,P=0.234>0.05). P+、P- allele frequencies are 0.510 vs0.628, 0.490vs0.372, without statistical significance(P>0.05).5 A multivariate logistic regression analysis, with a =0.1 as the selective and exclusive criterion. The dependent variable was getting the ACI or not and the independent variables included hypertension, diabetes, smoking, carrying P+ allele, obesity(BMI) and other risk factors for ACI. It is found that smoking history, hypertension, diabetes were brought into the model, as independent risk factors for ACI; while carrying P+ allele was not.6 N291S mutation of LPL was not found in either group.Conclusion1 The allele P+ had no significant correlation with serum triglyceride levels.2 The allele P+, which had no association with ACI, couldn’t be regarded as one of the independent genetic risk factors for ACI in Chinese population.3 N291S mutation of LPL, which had certain association with HTG and ACI in European Whites, was not found in either group. Maybe it is not associated with Chinese incidence of HTG and ACI.4 History of smoking, hypertension and diabetes were independent risk factors for ACI respectively, which is in line with the understanding of the past.5 The study found no direct correlation between obesity and the incidence of ACI.更多还原