阻塞性睡眠呼吸暂停综合征患者纤维蛋白原Bβ448和纤溶酶原激活物抑制物-1 4G/5G基因多态性分析

The polymorphisms of Fg Bβ448 and PAI-1 4G/5G in patients with obstructive sleep apnea-hypopnea syndrome

目的 研究阻塞性睡眠呼吸暂停综合征 (OSAHS)患者纤维蛋白原 (Fg)含量与FgBβ448位点基因多态性及mRNA表达的关系 ,以及OSAHS患者纤溶酶原激活物抑制物 1(PAI 1 )活性 (PAI 1∶A)及含量 (PAI 1∶Ag)与PAI 1 4G/ 5G基因多态性及mRNA表达的关系。方法 依据睡眠呼吸监测的结果 ,将实验对象分为正常对照组与OSAHS组 ,分别测定其血浆Fg含量、PAI 1∶A、PAI 1∶Ag和FgBβ448位点、PAI 1 4G/ 5G基因多态性 (RFLP)及mRNA表达 (cDNA合成 )。结果 OSAHS患者FgBβ448位点A/A基因型出现频率显著低于对照组 ,A/L +L/L基因型出现频率显著高于对照组。不同基因型对FgmRNA表达有不同的影响 ,其中L/L基因型mR NA表达最高 ,其次为A/L基因型 ,A/A基因型mRNA表达最低。FgmRNA的表达量与血浆Fg水平呈显著正相关 ;OSAHS患者PAI 1 4G/ 4G +4G/ 5G基因型出现频率显著高于对照组。不同基因型对PAI 1mRNA表达的影响各异 ,其中 4G/ 4G基因型mRNA表达最高 ,其次为 4G/ 5G基因型 ,5G/ 5G基因型mRNA表达最低。FgmRNA的表达量与血浆PAI 1∶A及PAI 1∶Ag水平呈显著正相关。结论 OSAHS患者存在凝血系统功能亢进和纤溶系统功能降低 ,可能是其易于罹患心血管系统疾病的原因之一 ,但OSAHS与心血管疾病及其危险因素之间的相互关系尚待进?

Objective The aim of this study was to study the relationships between the Fg Bβ448 polymorphisms and their mRNA expression and fibrinogen(Fg) level, and the relationships between plasminogen activator inhibitor 1(PAI 1) 4G/5G polymorphisms and their mRNA expression and PAI 1 activity(PAI 1∶A),PAI 1 antigen (PAI 1∶Ag)level in patients with obstructive sleep apnea hypopnea syndrome(OSAHS) Methods Based on the results of sleep monitoring,the subjects were divided into two groups:healthy control group and OSAHS group The contents of Fg,PAI 1∶A and PAI 1∶Ag in plasma were detected The Fg Bβ448 and the PAI 1 4G/5G polymorphisms were analysed Results The frequency of A/A genotype of Fg Bβ448 were lower in OSAHS group than that in control group,while A/L+L/L were higher in OSAHS group This polymorphism was associated with elevated Fg mRNA expression and a positive correlation between mRNA expression and plasma Fg level was demonstrated The frequency of 4G/4G+4G/5G genotype of PAI 1 were significantly higher in OSAHS group than that in control group,in the same way,contributing to PAI 1 mRNA overexpression There existed positive correlation between mRNA expression and the plasma PAI 1∶A and PAI 1∶Ag levels Conclusions Higher frequency of L/L,A/L,4G/4G,4G/5G genetic polymorphism were observed in OSAHS group with overexpression of mRNA and protein in plasma The patients with OSAHS with these genetic characters were supposed to be at high risk for cardiovascular diseases due to hypercoagulation and fibrinolysis deficiency,so Fg Bβ448 and PAI 1 4G/5G polymorphisms with mRNA and protein expression should be valuable predictive indices,otherwise their exact impact need further studies