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

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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。 Objective To investigate the relationship between 4G / 5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene promoter region and Kawasaki disease (KD) in Chinese Han children. Methods A total of 126 children with KD from 2001 to 2003 in Shenzhen Children’s Hospital were enrolled in this study. Allele-specific polymerase chain reaction (AS-PCR) was used to detect the promoter region of PAI-1 in 126 children and 120 healthy children 4G / 5G polymorphism; PAI-1 plasma activity was detected by chromogenic substrate method. Results (1) Plasma PAI-1 activity in children with KDⅠgroup (with coronary artery injury) and KDⅡgroup (without coronary artery injury) were significantly higher than those in healthy control group (all P <0.05). The plasma level of PAI-1 in KDⅠgroup was higher than that in KDⅡgroup (t = 9.78, P <0.05). (2) The plasma levels of 4G / 4G genotype PAI-1 in KDⅠand KDⅡgroups were significantly higher than those in 4G / 5G and 5G / 5G genotypes (all P <0.05). (3) The frequency of 4G / 4G genotype in KDⅠgroup was significantly higher than that in KDⅡgroup (P <0.05) and healthy control group (P <0.05). The odds ratio (OR) of the 4G / 4G homozygote genotype to KD coronary complications was 2.80 (95% CI: 1.25-6.29, P <0 · 05). Conclusions The 4G / 5G polymorphism of PAI-1 gene promoter is closely related to KD coronary artery injury. The 4G / 4G genotype of PAI-1 gene promoter may be used as a genetic marker for KD coronary artery atherosclerosis.
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