Sequence variations in the FII, FV, F13A1, FGB and PAI-1 genes are associated with differences in myocardial perfusion.
ABSTRACT Coronary artery disease (CAD) is a significant cause of morbidity and mortality in modern societies. The association between genetic markers and CAD is still poorly understood. In this study, we evaluated the effect of five genetic variants: Factor V Leiden (FV:c.1691G>A) (rs6025), Factor II prothrombin (FII:c.20210G>A; rs1799963), plasminogen activator inhibitor 1 (PAI-1) -675(4G/5G; SERPINE1:g.4329_4330insG; rs34857375), β-fibrinogen -455G>A (FGB:c.4577G>A; rs1800790) and Factor XIII (F13A1:c.103G>T; rs5985) on myocardial perfusion.
We examined 523 patients using exercise-rest myocardial perfusion single photon emission computed tomography, where the summed stress score (SSS), summed rest score and summed difference score (SDS) indexes, were calculated. In order to examine the independent prognostic ability of genotype on SSS and SDS, multiple linear regression models were used.
It was found that Factor V Leiden, Factor XIII, β-fibrinogen and PAI-1 genotypes were independent prognostic predictors of SSS and SDS with Factor XIII exhibiting the strongest association. Moreover, Factor II prothrombin proved an independent prognostic predictor of SSS.
Our study provides the first evidence of an association between these polymorphisms and myocardial perfusion, suggesting that the process of coronary artery disease and also patients' prognosis, may be modified by the FV:c.1691G>A, FII:c.20210G>A, PAI-1 -675 (4G/5G), β-fibrinogen FGB:c.4577G>A and F13A1:c.103G>T genotypes.
SourceAvailable from: Ioannis TsougosCoronary Angiography - Advances in Noninvasive Imaging Approach for Evaluation of Coronary Artery Disease, 09/2011; , ISBN: 978-953-307-675-1
[Show abstract] [Hide abstract]
ABSTRACT: Objective: To clarify the relationship between a stress-related marker, plasminogen activator inhibitor (PAI)-1, and a history of alcohol abuse in the childhood home. Methods: We compared the serum levels of PAI-1 between individuals with a history of alcohol abuse in the childhood home (N=53) and controls without such a history (N=96) in a population-based sample of adults with a high level of mental symptoms. Results: Subjects who experienced alcohol abuse in the childhood home had lower levels of PAI-1 (p=0.011) and more often a diagnosis of major depressive disorder (MDD) (p < 0.001) when compared with the controls. In multivariate analyses, lowered levels of PAI-1 were associated with an approximately doubled likelihood of belonging to the group with alcohol abuse in the childhood home in three different models with adjustments for age, gender, body mass index, MDD, coronary heart disease and cholesterol medication (ORs 2.19-2.43; p ≤ 0.05 in all models). Conclusion: A history of alcohol abuse in the childhood home was independently associated with lowered levels of PAI-1, a substance with neuroprotective qualities. Lowered PAI-1 in individuals who experience alcohol abuse in the childhood home may increase their vulnerability to neuronal pathology closely related to psychiatric symptoms.
[Show abstract] [Hide abstract]
ABSTRACT: Despite dual antiplatelet therapy, stent thrombosis remains a devastating and unpredictable complication of percutaneous coronary intervention (PCI). To perform a sequential analysis of clinical and genetic factors associated with definite early stent thrombosis. Case-control study conducted in 10 centers in France between January 2007 and May 2010 among 123 patients undergoing PCI who had definite early stent thrombosis and DNA samples available, matched on age and sex with 246 stent thrombosis-free controls. Accuracy of early stent thrombosis prediction by 23 genetic variants. Among the 23 genetic variants investigated in 15 different genes, the significant determinants of early stent thrombosis were CYP2C19 metabolic status (adjusted odds ratio [OR], 1.99; 95% CI, 1.47-2.69), ABCB1 3435 TT genotype (adjusted OR, 2.16; 95% CI, 1.21-3.88), and ITGB3 PLA2 carriage (adjusted OR, 0.52; 95% CI, 0.28-0.95). Nongenetic independent correlates were acuteness of PCI (adjusted OR, 3.05; 95% CI, 1.54-6.07), complex lesions (American College of Cardiology/American Heart Association type C) (adjusted OR, 2.33; 95% CI, 1.40-3.89), left ventricular function less than 40% (adjusted OR, 2.25; 95% CI, 1.09-4.70), diabetes mellitus (adjusted OR, 1.82; 95% CI, 1.02-3.24), use of proton pump inhibitors (adjusted OR, 2.19; 95% CI, 1.29-3.75), and higher clopidogrel loading doses (adjusted OR, 0.73; 95% CI, 0.57-0.93). The discriminative accuracy of the clinical-only model was similar to that of a genetic-only model (area under the curve, 0.73 [95% CI, 0.67-0.78] vs 0.68 [95% CI, 0.62-0.74], respectively; P = .34). A combined clinical and genetic model led to a statistically significant increase in the discriminatory power of the model compared with the clinical-only model (area under the curve, 0.78 [95% CI, 0.73-0.83] vs 0.73 [95% CI, 0.67-0.78]; P = .004). This case-control study identified 3 genes (CYP2C19, ABCB1, and ITGB3) and 2 clopidogrel-related factors (loading dose and proton pump inhibitors) that were independently associated with early stent thrombosis. Future studies are needed to validate the prognostic accuracy of these risk factors in prospective cohorts.JAMA The Journal of the American Medical Association 10/2011; 306(16):1765-74. DOI:10.1001/jama.2011.1529 · 30.39 Impact Factor