The association between plasminogen activator inhibitor type 1 (PAI-1) levels, PAI-1 4G/5G polymorphism, and myocardial infarction: A mendelian randomization meta-analysis
ΣυγγραφέαςNikolopoulos, Georgios K.
Bagos, Pantelis G.
Tsiara, Chrissa G.
Tsantes, Argirio E.
SourceClinical Chemistry and Laboratory Medicine
Google Scholar check
MetadataΕμφάνιση πλήρους εγγραφής
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.
Showing items related by title, author, creator and subject.
Generalized least squares for assessing trends in cumulative meta-analysis with applications in genetic epidemiology Bagos, Pantelis G.; Nikolopoulos, Georgios K. (2009)Objective: Cumulative meta-analysis allows the evaluation of a study's contribution to the combined effect of the preceding research. It accrues evidence, gradually adding studies one at a time and provides updated estimates ...
Spectral density ratio based clustering methods for the binary segmentation of protein sequences: A comparative study Ioannou, Androulla; Fokianos, Konstantinos; Promponas, Vasilis J. (2010)We compare several spectral domain based clustering methods for partitioning protein sequence data. The main instrument for this exercise is the spectral density ratio model, which specifies that the logarithmic ratio of ...
Mixed-effects poisson regression models for meta-analysis of follow-up studies with constant or varying durations Bagos, Pantelis G.; Nikolopoulos, Georgios K. (2009)We present a framework for meta-analysis of follow-up studies with constant or varying duration using the binary nature of the data directly. We use a generalized linear mixed model framework with the Poisson likelihood ...