纤溶酶原激活物抑制物 1基因启动子区4G/5G多态性与川崎病冠状动脉损伤的关系

目的探讨纤溶酶原激活物抑制物 1(PAI 1)基因启动子区4G/5G多态性与中国汉族儿童川崎病(KD)的关系。 方法对2001—2003在深圳市儿童医院就诊的KD患儿126例，用等位基因特异性聚合酶链反应(AS PCR)检测126例患儿和120名健康儿童PAI 1基因启动子区4G/5G多态性；用发色底物法检测各组PAI 1血浆活性。 结果(1)KDⅠ组(合并冠状动脉损伤)和KDⅡ组(无冠状动脉损伤)患儿PAI 1血浆活性均高于健康对照组，差异有显著性(P均<005)。KDⅠ组PAI 1血浆活性高于KDⅡ组，差异有显著性(t=978，P<005)。(2)KDⅠ组和KDⅡ组中4G/4G基因型PAI 1血浆活性明显高于4G/5G基因型和5G/5G基因型，差异有显著性(均P<005)。(3)KDⅠ组4G/4G基因型频率显著高于KDⅡ组(P<005)和健康对照组(P<005)。与非4G/4G纯合子基因型相比，4G/4G纯合子基因型对KD冠状动脉并发症的比值比(OR)为280(95%置信区间：125~629，P<005)。 结论PAI 1基因启动子区4G/5G多态性与KD冠状动脉损伤密切相关，PAI 1基因启动子区4G/4G基因型可作为KD冠状动脉损伤高危人群的基因标志。

Correlation between Kawasaki disease and 4G/5G polymorphism of plasminogen activator inhibitor 1 gene promoter.

AbstractObjectiveTo investigate the genetic association of the PAI 1 promoter 4G/5G polymorphism in juvenile Hans nationality patients with KD. MethodsFrom 2001 to 2003 4G/5G polymorphism of PAI 1 gene promoter from 126 children with KD was determined by allele specific polymerase chain reaction(AS PCR),and 120 age matched normal children from the Han nationality were used as control.The plasma PAI 1 activity was assayed by ELISA.All patients were performed Doppler echocardiography examination in order to differentiate coronary artery lesion(CAL). ResultsThe plasma PAI 1 activity level in two KD groups were significantly higher than those in normal controls group(P<005);the plasma PAI 1 activity level in the KD I group(with CAL) was significantly higher than those in the KD II group(without CAL)( P<001).PAI 1 level in 4G homozygous genotype was significantly higher than 4G/5G heterozygous genotype and 5G homozygous genotype in two KD groups (P<005).The 4G/4G genotype frequency in KD I group was significantly higher than those in KD II group(P<005) and normal controls group(P<005).The 4G/4G homozygous genotype of PAI 1 was significantly associated with CAL caused by KD(OR=280,95%confidence interval 125~629,P<005). ConclusionThe 4G/5G polymorphism of PAI 1 gene promoter might be related to the coronary artery complication of KD and 4G/4G homozygous genotype might be regarded as a genetic marker of risk factor for CAL in KD.