普伐他汀治疗过程中ABCA1基因变异对心脏病患者的影响

Significance of ABCA1 Gene Mutation of Pravastatin Therapy on the Patients with Heart Disease

关键词:  普伐他汀  ABCA1基因变异  冠心病

Key words:  pravastatin therapy  ABCA1 gene mutation  coronary heart disease

摘要:

目的 研究普伐他汀治疗过程中ABCA1基因变异对心脏病患者的影响。方法 选取236例冠心病(coronary heart disease，CHD)患者与267例健康体检者(设为对照组)。CHD患者分为常规治疗组和普伐他汀组，常规治疗组口服阿司匹林0.1 g·d^-1，普伐他汀组在口服阿司匹林0.1 g·d^-1的基础上给予普伐他汀35 mg·d^-1，抽血检测患者治疗前、治疗8、16周后的总胆固醇(total cholesterol，TC)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol，HDL-C)、载脂蛋白A-I(apoprotein A-I，apoA-I)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol，LDL-C)、载脂蛋白B(apoprotein B，apoB)和三酰甘油(triacylglycerol，TG)水平，提取DNA进行基因型分析。对照组抽血检测6项生化指标，采用Taqman探针技术提取DNA并进行基因型分析。结果 CHD患者吸烟者139例显著高于对照组116例；ABCA1 R219K基因变异频率两者相似，K携带者所占比率：CHD组为67.8%，对照组为66.7%；普伐他汀组治疗8，16周后较常规治疗组的TC、TG、LDL-C、apoB水平低，HDL-C、apoA-I水平高，差异具有统计学意义(P<0.05)；CHD患者中K携带者HDL-C、apoA-I水平高于RR型，TG水平低于RR型，普伐他汀治疗前后LDL-C、apoB、TC水平在RR、RK、KK 3种基因型组间差异无统计学意义；治疗前后K携带患者的HDL-C以及apoA-I水平显著高于RR基因型患者(P<0.05)；ABCA1基因变异对普伐他汀治疗疗效有促进作用，尤其KK基因型与RR型相比，具极显著促进作用(P=0.008)。结论 ABCA1基因变异影响冠心病患者血浆脂质水平，尤其是HDL-C和apoA-I的水平。

Abstract:

OBJECTIVE To study the significance of ABCA1 gene mutation of pravastatin therapy on the patients with heart disease. METHODS Two hundred and thirty six cases of coronary heart disease(CHD) patients and 267 cases of healthy subjects were selected. CHD patients were divided into CHD-conventional treatment group and CHD-ravastatin group. CHD-conventional treatment got aspirin 0.1 g·d^-1, CHD-ravastatin got pravastatin 35 g·d^-1 plus aspirin 0.1 g·d^-1. The level of TC, HDL-C, apoA-I, LDL-C, apoB, TG in blood samples were tested before and after treated for 8, 16 weeks. Control group also adopted 6 biochemical index of blood testing, and DNA in two groups was extracted by Taqman probe method for genotype analysis. RESULTS The number of smoking in CHD group(139 cases) was significantly higher than that of control group (116 cases); ABCA1 R219K gene mutation frequency was similar in the two groups, K carriers ratio in CHD and control group were 67.8% and 66.7%. Compared with CHD-conventional treatment group, after 16 weeks treatment, CHD-ravastatin group had lower level of TC, TG, LDL-C, apoB and higher level of HDL-C and apoA-I. The change regulation of after 8 weeks treatment was the same, the difference was statistically significant (P<0.05). K carriers of CHD group had higher HDL-C, apoA-I level and lower TG level, and LDL-C, apoB, TC level in RR, RK, KK genotypes had no differences before and after pravastatin therapy. The HDL-C, apoA-I level of K carriers were significantly higher than RR type(P<0.05); ABCA1 gene mutation promoted the curative effect of pravastatin therapy. CONCLUSION ABCA1 gene mutation has effects on CHD patients’ blood plasma lipid level, especially HDL-C and apoA-I level.