湖北地区汉族人群动脉硬化性脑梗死与载脂蛋白(a)5''''调控区(TTTTA)n基因多态性的关系

背景载脂蛋白(a)具有促进动脉粥样硬化斑块形成的作用,在载脂蛋白(a)5'存在一个五核苷酸重复序列(pentanuclotiderepeats,PNR),对研究遗传和预测动脉硬化性脑梗死(atherosclerosis cerebralinfarction,ACI)的危险性具有一定的价值,但在不同人种中与ACI的关系尚处在探索阶段,载脂蛋白(a)PNR基因多态性在汉族人群ACI发病中的意义如何?目的研究载脂蛋白(a)PNR基因多态性与ACI的关系.设计以湖北地区汉族ACI患者和正常人群为研究对象的病例-对照研究.单位一所大学医院的检验科.对象选择1998-02/1999-03武汉大学中南医院和武汉大学亚太医院神经内科确诊的ACI患者82例(ACI组)及健康体检者153例(对照组),均为无血缘关系的湖北地区汉族人.方法对所有受试者分别检测血清脂蛋白(a)、总胆固醇、高密度脂蛋白胆固醇(highdensity lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(ligh densitylipoprotein cholesterol,LDL-C)、三酰甘油、载脂蛋白AⅠ及载脂蛋白B水平.同时采用聚合酶链反应结合高压聚丙烯酰胺凝胶电泳检测载脂蛋白(a)5'调控区五核苷酸重复序列基因多态性,并加以对照分析.结果ACI患者脂蛋白(a)[(239.9±2254)mg/L]、总胆固醇[(4.76±0.74)mmol/L]、三酰甘油[(1.74±0.60)mmol/LI、LDL-C[(2.84±0.63)mmol/L]水平明显高于对照组[(133.5±97.7)mg/L,(4.29±0.72)mmol/L,(1.05±0.52)mmol/L,(2.84±0.63)mmol/L],HDL-C水平[(0.88±0.17)mmol/L]明显低于对照组[(1.03±0.35)mmol/L],差异均有显著性意义(t=3.65～9.18,P均＜0.01),载脂蛋白AⅠ[(1.13±0.15)和(1.25±0.19)mmol/L]、载脂蛋白B[(0.93±0.12)和(0.89±0.15)mmol/L],与对照组比较差异无显著性意义;ACI组中重复序列数为5的等位基因频率(0.098)明显高于正常对照组(0.026),差异有显著性意义(x2=5.62,P＜0.05),重复序列数为9的等位基因频率(0.073)明显低于对照组(0.213),差异有显著性意义(x2=7.83,P＜0.01),且重复序列数为5的等位基因还与血浆TC下降和Lp(a)升高有关联.结论提示Apo(a)PNR基因多态性与人群易感ACI有关,可能在一定程度上参与ACI的发生和发展过程.

Relationship between (TTTTA)n gene polymorphism in the apolipoprotein(a) 5'''' control region and atherosclerotic cerebral infarction in Han nationality of Hubei area

BACKGROUND: Apolipoprotein(a) [Apo(a)] plays some role in promoting the formation of atherosclerotic plaque, and contains pentanucleotide repeats(PNR), which has a key value in genic research and in forecast on the increased risk of early atherosclerosis cerebral infarction (ACI). But the relationship between ACI and Apo(a) PNR in different races needs to be further investigated.OBJECTIVE: To investigate the relationship between the Apo(a) PNR polymorphism and ACI.DESIGN: A case-control study based on the ACI patients and normal people of Han nationality in Hubei.SETTING: Department of Laboratory in a hospital of a university.PARTICIPANTS: From February 1998 to March 1999, 82 ACI patients (ACI group) and 153 healthy controls(control group) were selected from the Department of Neurology, Central South Hospital and Yatai Hospital of Wuhan University. All patients were Han nationality in Hubei without any relatives.METHODS: Serum lipoprotein(a) [Lp(a) ], total cholesterol(TC), high density lipoprotein cholesterol(HDL-c), low density lipoprotein cholesterol (LDL-c), triglyceride (TG), apolipoprotein A Ⅰ (ApoA Ⅰ) and apolipoprotein B (Apo B) were tested respectively. Meanwhile, the PNR in the 5' control region of the Apo(a) was detected with polymerase chain reaction(PCR) and high voltage polyacrylamide gels electrophoresis. The results were analyzed with controlled analysis.RESULTS: The levels of serum Lp(a) [ (239.9 ±225.4) mg/L], TC [(4.76±0.74) nmol/L], TG[(1.74±0.60) mmol/L] and LDL-C [ (2.84 ± 0. 63) mmol/L] were remarkably higher in ACI group than those in control group, which were(133.5 ±97.7) mg/L in serum Lp(a), (4. 29±0.72) mmol/L in TC, (1.05±0.52) mmol/L in TG and(2.84±0.63) mmol/L in LDL-C, however, the level of HDL-C[ (0.88± 0.17) mmol/L] was remarkably lower in ACI group than that in control group [ ( 1.03 ± 0. 35 ) mmol/L], the differences were all significant( t = 3.65to9.18, P ＜ 0.01) . The levels of ApoA Ⅰ [(1.13±0.15) mmol/L,(1.25±0.19) mmol/L] and ApoB[(0.93±0.12) mmol/L, (0.89± 0. 15 ) mmol/L] were no significant difference compared with those in control group. The duplicated frequency of the allele(TTTTA) 5(0. 098) in the ACI was remarkably higher than that in control(0. 026) (x2 = 5.62, P＜ 0. 05), The frequency of the allele(TTTTA) 9 in the ACI(0. 073) was remarkably lower than that in control (0. 213 ) (x2 = 7.83, P ＜ 0.01 ), The frequency of the allele(TTTTA) 5 was also associated with low TC and high Lp(a) levels.CONCLUSION: It is suggested that the Apo(a) PNR polymorphism are associated with the susceptibility to ACI, and involved in the development of ACI.