脂蛋白脂酶PvuⅡ基因位点多态性与动脉粥样硬化性脑梗死的关系

The relationship between lipoprotein lipase gene polymorphism at PvuⅡ locus and atherosclerotic cerebral infarction

目的探讨脂蛋白脂酶(LPL)PvuⅡ基因位点多态性与动脉粥样硬化性脑梗死发病的关系及其对血脂、颈动脉斑块的影响。方法选择动脉粥样硬化性脑梗死患者166例,根据患者入院时美国国立卫生研究所卒中评分,将脑梗死分为轻型(70例)、中型(87例)和重型(9例)3个亚组;按照TOAST分类,分为大血管受累组(37例)及小血管受累组(129例)。另外选择72名健康成人为对照组。采用聚合酶链反应-限制性片段长度多态性方法,进行LPLPvuⅡ基因多态性分析;酶法测定血脂;颈动脉超声多普勒检查颈总动脉内膜中层厚度(IMT)及颈动脉斑块(CAP),并据此进行分级。结果脑梗死组P+P+、P-P+及P-P-基因型患者血浆三酰甘油分别为(2.0±1.4)、(1.5±1.0)及(1.3±0.6)mmol/L,P+P+与P-P+、P-P-基因型相比差异有统计学意义(P=0.027,P=0.001);高密度脂蛋白胆固醇(HDL-C)分别为(0.99±0.25)、(1.10±0.29)及(1.48±0.68)mmol/L,差异亦有统计学意义(P=0.023,P=0.01);大小血管受累组、不同病情组及不同CAP分级患者的基因型分布,差异无统计学意义。脑梗死组P+等位基因频率为66.6%,对照组为47.9%(P=0.000);脑梗死组、对照组组内各基因型之间左右颈总动脉IMT差异无统计学意义。结论LPLPvuⅡ基因位点多态性与血脂变化及脑梗死的关系密切,P+P+基因型与血浆三酰甘油升高,HDL-C下降有关;P+P+基因型可能是脑梗死的易感基因。

Objective To explore the relationship between lipoprotein lipase （LPL） gene polymorphism at Pvu Ⅱ locus and atherosclerotic cerebral infarction （CI） and its effect on plasma lipids and carotid artery plaque （CAP）. Methods A total of 166 patients with atherosclerotic CI were recruited. According to National Institutes of Health Stroke Scale scores. All patients were divided into 3 groups： the mild infarction group （ n =70）, the moderate infarction group （ n = 87 ）, and the severe infarction （ n = 9 ）. According to the TOAST classification, they were divided into major vessel involved group （ n = 37） and minor vessel involved group （n = 129）. Another 72 healthy adults were selected as control group. The analysis of LPL gene polymorphism at Pvu Ⅱ locus was performed by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） ; the plasma lipids were measured by enzymatic method; the carotid intima-media thickness （IMT） and CAP were detected with carotid uhrasonagraphic Doppler and were thus graded. Results The plasma triglyceride levels of P＋P＋ , P-P＋ and P-P- genotype carriers in the CI group were 2.0 ±1.4, 1.5 ± 1.0, and 1.3 ±0. 6 mmol/L, respectively, and there were significant differences between P＋P＋ and P-P＋ , P-P- （P =0. 027, P =0. 001 ）. Their high density lipoprotein cholesterol levels were 0. 99 ±0. 25, 1, 10 ± 0. 29, and 1.48 ±0. 68 mmol/L in the P＋P＋ , P-P＋ and P-P- group, respectively, and there were also significant differences between P＋P＋ and P-P＋ ,P-P- group （P = 0. 023, P = 0. 01 ） ; the genotype distribution did not have significant differences between the major and minor vessel involved groups, different conditions, and different CAP graded patients. The frequency of P＋ allele was 66. 6% in the CI group, and 47. 9% in the control group （P =0. 000）. There were no significant differences among all genotypes both at left and right common carotid arteries in the CI and control groups. Conclusion LPL gene polymorphism at Pvu Ⅱ locus is closely correlated with the changes of plasma lipids and CI. P＋P＋ genotypes are associated with the increase of plasma triacylglycerol and the decrease of plasma high density lipoprotein cholesterol. P＋P＋ genotypes may be the susceptible genotypes of CI.