Liu Xiaoning, Sun Li, Li Zhaohui, Gao Yan, Hui Rutai
Sino-German Laboratory for Molecular Medicine, Fuwai Cardiovascular Hospital, Chinese Academy of Medical Sciences. Beijing 100037, China.
Zhonghua Yi Xue Za Zhi. 2002 Oct 25;82(20):1396-400.
Investigate the distribution and characteristics of 5'pentanucleotide TTTTA repeat (PNTR) polymorphism of apolipoprotein (a) [apo (a)] gene among Chinese patients with myocardial infarction (MI) and cerebral infarction, and its relationship to plasma lipoprotein (a) [Lp (a)] level.
DNA was extracted from the peripheral blood of 438 patients with myocardial infarction (MI, documented angiographically) and 218 controls, and 809 patients with cerebral infarction (documented by CT) and 1 817 controls. Plasma Lp (a) level was measured by ELISA. PNTR polymorphism of apo (a) gene was determined by polymerase chain reaction (PCR) and subsequent polyacrylamide gel electrophoresis.
Eight alleles and 29 genotypes in apo (a) PNTR were detected in the four groups. The frequency of (TTTTA)(4 - 7) allele in the cerebral infarction group was 7.0%, significantly higher than that in control group (5.4%, P < 0.05). The frequency of genotype (TTTTA)(5/8) in MI group was 13.2%, significantly higher than that in the control group (7.8%, P < 0.05). No significant difference was seen in other alleles and genotypes among different groups (all P > 0.05). The level of triglyceride (TG) in patients with MI was 5.13 mmol/L +/- 1.15 mmol/L, significantly higher than that in controls (4.90 mmol/L +/- 0.99 mmol/L, P < 0.05). The level of TG in patients with cerebral infarction was 1.84 mmol/L +/- 1.36 mmol/L, not significantly different from that in controls (1.83 mmol/L +/- 1.51 mmol/L). The level of total cholesterol (TC) in patients with MI was 4.85 mmol/L +/- 1.04 mmol/L, significantly lower than that in controls (4.97 mmol/L +/- 1.00 mmol/L, P < 0.001). The level of TC in patients with cerebral infarction was 1.97 +/- 1.11 mmol/L, not significantly different from that in controls (1.79 mmol/L +/- 1.23 mmol/L). A negative correlation between the number of PNTR and Lp (a) level was observed in both MI group (P < 0.001) and cerebral infarction group (P < 0.01), and not in the control group. Small fragment repeat of apo (a) PNTR was correlated with cerebral infarction (OR = 1.4, 95% CI: 1.040 approximately 1.910), not significantly with MI (P > 0.05). Multiple logistic regression analysis showed that individuals with plasma Lp (a) > 300 mg/L had higher risk of MI (OR = 2.4, 95% CI: 1.630 - 3.594), and a higher risk of cerebral infarction (OR = 1.6, 95% CI: 1.013 - 2.021) after adjustment for age, sex, SBP, DBP, BMI, smoking, TC, TG, HDL-C, LDL-C and Glu.
Plasma Lp (a) is an independent risk factor for MI and cerebral infarction. PNTR of apo (a) gene was negatively correlated with Lp (a) levels both in MI group and cerebral infarction group. Association with PNTR genotype was only found in cerebral infarction, but not in MI.
研究载脂蛋白(a)[apo(a)]基因5'五核苷酸TTTTA重复序列(PNTR)多态性在中国心肌梗死(MI)和脑梗死患者中的分布及特征，及其与血浆脂蛋白(a)[Lp(a)]水平的关系。
从438例经血管造影证实的心肌梗死患者及218例对照者的外周血中提取DNA，以及809例经CT证实的脑梗死患者及1817例对照者的外周血中提取DNA。采用酶联免疫吸附测定法(ELISA)检测血浆Lp(a)水平。采用聚合酶链反应(PCR)及随后的聚丙烯酰胺凝胶电泳法检测apo(a)基因的PNTR多态性。
四组中检测到apo(a)PNTR的8个等位基因和29种基因型。脑梗死组中(TTTTA)(4 - 7)等位基因频率为7.0%，显著高于对照组(5.4%，P<0.05)。MI组中基因型(TTTTA)(5/8)频率为13.2%，显著高于对照组(7.8%，P<0.05)。不同组间其他等位基因和基因型未见显著差异(均P>0.05)。MI患者甘油三酯(TG)水平为5.13 mmol/L±1.15 mmol/L，显著高于对照组(4.90 mmol/L±0.99 mmol/L，P<0.05)。脑梗死患者TG水平为1.84 mmol/L±1.36 mmol/L，与对照组(1.83 mmol/L±1.51 mmol/L)无显著差异。MI患者总胆固醇(TC)水平为4.85 mmol/L±1.0 ,4 mmol/L，显著低于对照组(4.97 mmol/L±1.00 mmol/L，P<0.001)。脑梗死患者TC水平为1.97±1.11 mmol/L，与对照组(1.79 mmol/L±1.23 mmol/L)无显著差异。MI组和脑梗死组中均观察到PNTR数目与Lp(a)水平呈负相关(P<0.001和P<0.01)，而对照组中未观察到。apo(a)PNTR的小片段重复与脑梗死相关(比值比[OR]=1.4，95%可信区间[CI]：1.0401.910)，与MI无显著相关性(P>0.05)。多因素logistic回归分析显示，校正年龄、性别、收缩压、舒张压、体重指数、吸烟、TC、TG、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和血糖后，血浆Lp(a)>300 mg/L的个体发生MI的风险较高(OR=2.4，95%CI：1.6303.594)，发生脑梗死的风险也较高(OR=1.6，95%CI：1.013~2.021)。
血浆Lp(a)是MI和脑梗死的独立危险因素。MI组和脑梗死组中apo(a)基因的PNTR与Lp(a)水平呈负相关。仅在脑梗死中发现与PNTR基因型有关联，而在MI中未发现。
