Association of PAI-1 4G/5G and-844G/A Gene Polymorphisms and Changes in PAI-1/Tissue Plasminogen Activator Levels in Myocardial Infarction: A Case-Control Study
Association of PAI-1 4G/5G and-844G/A Gene Polymorphisms and Changes in PAI-1/Tissue Plasminogen Activator Levels in Myocardial Infarction: A Case-Control Study
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DOI：
10.1089/gtmb.2009.0039
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发表时间：
2010-02-01
影响因子：
1.4
通讯作者：
Mahjoub, Touhami
中科院分区：
文献类型：
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作者：
Abboud, Nesrine;Ghazouani, Lakhdar;Mahjoub, Touhami
背景：心肌梗死（MI）是由获得性和遗传性危险因素诱发的，包括纤溶酶原激活物抑制剂-1 (PAI-1) -844G/A和-675G/A （4G/5G）基因变异。目的：本研究的目的是探讨PAI-1- 844g /A和4G/5G多态性以及PAI-1和组织纤溶酶原激活物（tPA）水平在突尼斯人群心肌梗死中的变化之间的关系。方法：这是一项病例对照研究，涉及305例心肌梗死患者和328例无关健康对照。采用聚合酶链反应-限制性片段长度多态性（RFLP） （-844G/A）或聚合酶链反应-等位基因特异性扩增进行PAI-1基因分型。血清学检测PAI-1和tPA水平。结果：与tPA水平相比，病例的平均血浆PAI-1抗原水平高于对照组。PAI-1水平的升高在-844A和4G等位基因携带者中更为明显。患者中（突变）4G和-844A等位基因、4G/4G和-844A/-844A基因型频率显著高于对照组，（野生）5G和-844G等位基因、5G/5G和-844G/-844G基因型频率显著低于对照组。与对照组相比，患者中4G/-844A单倍型的患病率增加，而5G/-844G单倍型的患病率降低，从而分别赋予这些单倍型易感性和保护性。在控制了一些协变量后，回归分析证实了4G/4G和-844A/A与MI的独立关联。结论：本研究提示血浆PAI-1升高的4G和-844A携带者发生心肌梗死的风险明显高，且与tPA水平降低相关。
Background: Myocardial infarction (MI) is induced by acquired and inherited risk factors, including the plasminogen activator inhibitor-1 (PAI-1) -844G/A and -675G/A (4G/5G) gene variants. Objective: The aim of this study was to investigate the association between PAI-1-844G/A and 4G/5G polymorphisms and changes in PAI-1 and tissue plasminogen activator (tPA) levels in MI in a Tunisian population. Methods: This was a case-control study involving 305 patients with MI and 328 unrelated healthy controls. PAI-1 genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (RFLP) (-844G/A) or by polymerase chain reaction-allele specific amplification. PAI-1 and tPA levels were assayed by serological assays. Results: In contrast to tPA levels, mean plasma PAI-1 antigen levels were higher in cases than in control subjects. The elevation in PAI-1 levels was more pronounced in -844A and 4G allele carriers. Significantly higher frequencies of (mutant) 4G and -844A alleles and 4G/4G and -844A/-844A genotypes, and corresponding lower frequencies of (wildtype) 5G and -844G alleles and 5G/5G and -844G/-844G genotypes were seen in patients than in controls. Increased prevalence of 4G/-844A and decreased prevalence of 5G/-844G haplotypes were seen in patients than in controls, thereby conferring a susceptibility and protective nature to these haplotypes, respectively. Regression analysis confirmed the independent association of 4G/4G and -844A/A with MI, after controlling for a number of covariates. Conclusion: This study indicated that the risk of MI was notably high in 4G and -844A carriers with elevated plasma PAI-1 and were associated with reduced tPA levels.