冠心病合并阻塞性睡眠呼吸暂停低通气综合征患者纤溶酶原激活物抑制物-1启动子区4G/5G基因多态性分析

Polymorphisms of PAI-1 4G/5G in patients with coronary heart disease complicated with or without OSAHS

目的:研究冠状动脉粥样硬化性心脏病(冠心病)合并阻塞性睡眠呼吸暂停低通气综合征(obstructivesleepapnea-hypopneasyndrome,OSAHS)患者纤溶酶原激活物抑制物-1(plasminogenactivatorinhibitor-1,PAI-1)含量(PAI-1∶Ag)和活性(PAI-1∶A)与PAI-1启动子区4G/5G等位基因多态性及表达的关系。方法:确诊为冠心病的患者67例,依据睡眠呼吸监测的结果分为合并OSAHS组与不合并OSAHS组。另从同期体格检查的健康人群中选出60名,年龄与上述两组匹配,依据睡眠呼吸监测的结果分为正常对照组与OSAHS组。分别测定4组的血浆PAI-1∶A、PAI-1∶Ag与PAI-1启动子区4G/5G位点基因多态性及信使核糖核酸(messengerribonucleicacid,mRNA)表达。结果:冠心病合并OSAHS组5G/5G基因型出现频率显著低于对照组(38%比70%),4G/5G、4G/4G并4G/5G基因型出现频率显著高于对照组(53%比23%,63%比30%)。不同基因型对mRNA表达有不同的影响,其中4G/4G基因型mRNA表达最高(3.6±0.5),其次为4G/5G基因型(3.1±0.4),5G/5G基因型mRNA表达最低(1.2±0.8)。不同基因型mRNA的表达量与血浆PAI-1∶A和PAI-1∶Ag水平呈显著正相关。结论:冠心病合并OSAHS患者具有较高的4G/4G、4G/5G基因频率,具有较高的mRNA表达水平,PAI-1∶A、PAI-1∶Ag含量较高。

Objective:To study the relationships between the plasminogen activator inhibitor 1 (PAI 1) 4G/5G polymorphisms and their mRNA expression and PAI 1 activity (PAI 1∶A) and PAI 1 protein levels (PAI 1∶Ag) in patients with coronary heart disease (CHD) complicated with or without obstructive sleep apnea hypopnea syndrome (OSAHS). Methods:Based on the results of sleep monitoring,CHD patients were divided into OSAHS+CHD group and CHD group. The healthy subjects were divided into OSAHS group and control group. The PAI 1 polymorphisms,mRNA expression and plasma PAI 1∶A and PAI 1∶Ag levels were examined. Results:The frequency of 5G/5G genotype was lower in CHD+OSAHS group than that in control group (38%vs 70.0%),while 4G/4G,4G/4G and 4G/5G were higher in CHD+OSAHS group (53%vs 23%,63%vs 30%) than that in control group. Different genotypes had different effects on PAI 1 mRNA expression. There existed positive correlation between mRNA expression and plasma PAI 1∶A and PAI 1∶Ag levels. Conclusion:Higher frequencies of 4G/4G and 4G/5G genotype were observed in CHD+OSAHS group with higher mRNA expression and higher PAI 1∶A and PAI 1∶Ag levels in plasma. Patients with OSAHS may have higher prevalence of cardiovascular diseases. Further studies are needed to clarify the relationships between OSAHS and cardiovascular diseases.