The association between plasminogen activator inhibitor type 1 (PAI-1) levels, PAI-1 4G/5G polymorphism, and myocardial infarction: A mendelian randomization meta-analysis
Ημερομηνία
2014Συγγραφέας
Nikolopoulos, Georgios K.Bagos, Pantelis G.
Tsangaris, I.
Tsiara, Chrissa G.
Kopterides, Petros
Vaiopoulos, A.
Kapsimali, Violetta
Bonovas, Stefanos
Tsantes, Argirio E.
Source
Clinical Chemistry and Laboratory MedicineVolume
52Issue
7Pages
937-950Google Scholar check
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Εμφάνιση πλήρους εγγραφήςΕπιτομή
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 metaregression 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.
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