Abboud Nesrine, Ghazouani Lakhdar, Saidi Sarra, Ben-Hadj-Khalifa Sonia, Addad Fawzi, Almawi Wassim Y, Mahjoub Touhami
Research Unit of Hematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia.
Genet Test Mol Biomarkers. 2010 Feb;14(1):23-7. doi: 10.1089/gtmb.2009.0039.
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.
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.
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.
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 (wild-type) 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.
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.
心肌梗死（MI）由获得性和遗传性风险因素诱发，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。
本研究旨在调查突尼斯人群中PAI-1 -844G/A和4G/5G多态性与MI患者中PAI-1和组织纤溶酶原激活物（tPA）水平变化之间的关联。
这是一项病例对照研究，纳入305例MI患者和328名无亲缘关系的健康对照。PAI-1基因分型通过聚合酶链反应-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和tPA水平通过血清学检测进行测定。
与tPA水平相反，病例组平均血浆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（突变型）4G和-844A等位基因以及4G/4G和-844A/-844A基因型的频率显著高于对照组，而（野生型）5G和-844G等位基因以及5G/5G和-844G/-844G基因型的频率相应较低。与对照组相比，患者中4G/-844A单倍型的患病率增加，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。回归分析在控制了多个协变量后证实了4G/4G和-844A/A与MI的独立关联。
本研究表明，血浆PAI-1升高的4G和-844A携带者发生MI的风险显著较高，且与tPA水平降低有关。
