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The association between plasminogen activator inhibitor type 1 (PAI-1) levels, PAI-1 4G/5G polymorphism, and myocardial infarction: a Mendelian randomization meta-analysis
dc.creator | Nikolopoulos, G. K. | en |
dc.creator | Bagos, P. G. | en |
dc.creator | Tsangaris, I. | en |
dc.creator | Tsiara, C. G. | en |
dc.creator | Kopterides, P. | en |
dc.creator | Vaiopoulos, A. | en |
dc.creator | Kapsimali, V. | en |
dc.creator | Bonovas, S. | en |
dc.creator | Tsantes, A. E. | en |
dc.date.accessioned | 2015-11-23T10:41:13Z | |
dc.date.available | 2015-11-23T10:41:13Z | |
dc.date.issued | 2014 | |
dc.identifier | 10.1515/cclm-2013-1124 | |
dc.identifier.issn | 1434-6621 | |
dc.identifier.uri | http://hdl.handle.net/11615/31396 | |
dc.description.abstract | Background: The circulating levels of plasminogen activator inhibitor type 1 (PAI-1) are increased in individuals carrying the 4G allele at position -675 of the PAI-1 gene. In turn, overexpression of PAI-1 has been found to affect both atheroma and thrombosis. However, the association between PAI-1 levels and the incidence of myocardial infarction (MI) is complicated by the potentially confounding effects of well-known cardiovascular risk factors. The current study tried to investigate in parallel the association of PAI-1 activity with the PAI-1 4G/5G polymorphism, with MI, and some components of metabolic syndrome (MetS). Methods: Using meta-analytical Mendelian randomization approaches, genotype-disease and genotype-phenotype associations were modeled simultaneously. Results: According to an additive model of inheritance and the Mendelian randomization approach, the MI-related odd ratio for individuals carrying the 4G allele was 1.088 with 95% confidence interval (CI) 1.007, 1.175. Moreover, the 4G carriers had, on average, higher PAI-1 activity than 5G carriers by 1.136 units (95% CI 0.738, 1.533). The meta-regression analyses showed that the levels of triglycerides (p=0.005), cholesterol (p=0.037) and PAI-1 (p=0.021) in controls were associated with the MI risk conferred by the 4G carriers. Conclusions: The Mendelian randomization meta-analysis confirmed previous knowledge that the PAI-1 4G allele slightly increases the risk for MI. In addition, it supports the notion that PAI-1 activity and established cardiovascular determinants, such as cholesterol and triglyceride levels, could lie in the etiological pathway from PAI-1 4G allele to the occurrence of MI. Further research is warranted to elucidate these interactions. | en |
dc.source.uri | <Go to ISI>://WOS:000338852700011 | |
dc.subject | 4G/5G polymorphism | en |
dc.subject | Mendelian randomization | en |
dc.subject | meta-analysis | en |
dc.subject | myocardial | en |
dc.subject | infarction | en |
dc.subject | plasminogen activator inhibitor type 1 (PAI-1) | en |
dc.subject | CORONARY-ARTERY-DISEASE | en |
dc.subject | HEMOSTATIC GENE POLYMORPHISMS | en |
dc.subject | INSULIN-RESISTANCE SYNDROME | en |
dc.subject | PLASMA PAI-1 | en |
dc.subject | PROMOTER POLYMORPHISM | en |
dc.subject | COMMON | en |
dc.subject | POLYMORPHISM | en |
dc.subject | ISCHEMIC-STROKE | en |
dc.subject | 4G4G GENOTYPE | en |
dc.subject | RISK-FACTORS | en |
dc.subject | CUMULATIVE | en |
dc.subject | METAANALYSIS | en |
dc.subject | Medical Laboratory Technology | en |
dc.title | The association between plasminogen activator inhibitor type 1 (PAI-1) levels, PAI-1 4G/5G polymorphism, and myocardial infarction: a Mendelian randomization meta-analysis | en |
dc.type | journalArticle | en |
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