Naslov
Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease

Autori
Ci Song, Stephen Burgess, John D. Eicher, Christopher J. O'Donnell and Andrew D. Johnson

Izvornik
Journal of the American Heart Association (2047-9980) 6 (2017); 28550093, 7

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
coronary heart disease ■ genome‐wide association study ■ Mendelian randomization ■ plasminogen activator inhibitor type 1 ■ single nucleotide polymorphism

Sažetak
Background: Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association reflects a causal influence of PAI-1 on CHD risk. Methods and results: To evaluate the association between PAI-1 and CHD, we applied a 3-step strategy. First, we investigated the observational association between PAI-1 and CHD incidence using a systematic review based on a literature search for PAI-1 and CHD studies. Second, we explored the causal association between PAI-1 and CHD using a Mendelian randomization approach using summary statistics from large genome-wide association studies. Finally, we explored the causal effect of PAI-1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta-analysis, the highest quantile of blood PAI-1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17 ; 95% CI: 1.53, 3.07) in an age- and sex- adjusted model. The effect size was reduced in studies using a multivariable-adjusted model (odds ratio=1.46 ; 95% CI: 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI-1 level on CHD risk (odds ratio=1.22 per unit increase of log-transformed PAI-1 ; 95% CI: 1.01, 1.47). In addition, we also detected a causal effect of PAI- 1 on elevating blood glucose and high-density lipoprotein cholesterol. Conclusions: Our study indicates a causal effect of elevated PAI-1 level on CHD risk, which may be mediated by glucose dysfunction.

Izvorni jezik
Engleski

Znanstvena područja
Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

Napomena
Na ovome sam radu u svojstvu člana ICBP konzorcija

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