4G/5G Polymorphism of the plasminogen activator inhibitor-1 gene and risk of restenosis after coronary artery stenting

Deutsches Herzzentrum München and 1. Medizinische Klinik rechts der Isar, Technische Universität München, München, Germany.
American heart journal (Impact Factor: 4.46). 11/2003; 146(5):855-61. DOI: 10.1016/S0002-8703(03)00363-6
Source: PubMed


Plasminogen activator inhibitor-1 (PAI-1) has been proposed as a candidate risk factor for restenosis after coronary artery stenting. Transcription, level, and activity of PAI-1 are influenced by the 4G/5G polymorphism in the promoter region of PAI-1 gene. The polymorphism may therefore affect wound-healing processes in injured blood vessels and influence restenosis.
In 1850 consecutive patients, angiographic measures of restenosis and the clinical outcome at 30 days and 1 year after stent implantation were evaluated. Angiographic restenosis was defined as > or =50% diameter stenosis determined at follow-up angiography, performed 6 months after stenting. The 4G/5G genotypes were determined with TaqMan technique.
Among the patients, the frequency of the 4G allele was 0.55. Follow-up angiography was done in 84% of the patients. We observed restenosis in 32.5% of 4G/4G carriers, 32.2% of 4G/5G carriers, and 35.7% of 5G/5G carriers (P =.52). The occurrence of a major adverse event (death, myocardial infarction, or target vessel revascularization due to restenosis-induced ischemia) was 5.6% in 4G/4G carriers, 5.3% in 4G/5G carriers, and 4.6% in 5G/5G carriers at 30 days (P =.80), and 24.7% in 4G/4G carriers, 23.0% in 4G/5G carriers, and 26.2% in 5G/5G carriers at 1 year (P =.45).
The 4G/5G polymorphism of the PAI-1 gene is not associated with an increased risk of thrombotic and restenotic events after coronary artery stenting.

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    • "The relationship between PAI-1 4G/5G gene polymorphism and CAD risk is subject to much controversy worldwide. In 2003, Böttiger C et al. reported that 4G/5G polymorphism of the PAI-1 gene is not associated with an increased risk of thrombotic and restenotic events after coronary artery stenting in Germany [25]. In 2007, Sampaio MF et al. reported that acute myocardial infarction (AMI) is not associated with PAI-1 gene polymorphisms in young adults in Brazil [26]. "
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    ABSTRACT: The polymorphism of plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene has been indicated to be correlated with coronary artery disease (CAD) susceptibility, but study results are still debatable. The present meta-analysis was performed to investigate the association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population. A total of 879 CAD patients and 628 controls from eight separate studies were involved. The pooled odds ratio (OR) for the distribution of the 4G allele frequency of PAI-1 4G/5G gene and its corresponding 95% confidence interval (CI) was assessed by the random effect model. The distribution of the 4 G allele frequency was 0.61 for the CAD group and 0.51 for the control group. The association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population was significant under an allelic genetic model (OR = 1.70, 95% CI = 1.18 to 2.44, P = 0.004). The heterogeneity test was also significant (P<0.0001). Meta-regression was performed to explore the heterogeneity source. Among the confounding factors, the heterogeneity could be explained by the publication year (P = 0.017), study region (P = 0.014), control group sample size (P = 0.011), total sample size (P = 0.011), and ratio of the case to the control group sample size (RR) (P = 0.019). In a stratified analysis by the total sample size, significantly increased risk was only detected in subgroup 2 under an allelic genetic model (OR = 1.93, 95% CI = 1.09 to 3.35, P = 0.02). In the Chinese Han population, PAI-1 4G/5G gene polymorphism was implied to be associated with increased CAD risk. Carriers of the 4G allele of the PAI-1 4G/5G gene might predispose to CAD.
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    • "Mutation in PAI-1 and other serpin family genes are associated with disorders/ diseases such as abnormal bleeding, impairment of wound healing, emphysema, and cirrhosis (Diéval et al., 1991; Fay et al., 1997; Gilabert-Estelles et al., 2005, 2006; Lee et al., 1993; Schleef et al., 1989). Several studies demonstrated that the 4G/4G polymorphism in the PAI-1 gene locus at −675 bp upstream of the transcription start site is a risk factor for coronary artery disease as compared with a 4G/5G or 5G/5G polymorphism (Böttiger et al., 2003; Margaglione et al., 1998). Recently, however, a meta-analysis of 32 independent clinical studies demonstrated that 1) the 4G/4G polymorphism of PAI-1 gene is not associated with MI and coronary artery disease; and 2) that it has only a marginal association with atherosclerosis (Koch et al., 2010). "
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