ABCB1 p.Gly455Ala
| Predicted by SNAP2: | A: D (80%), C: D (66%), D: D (59%), E: D (85%), F: D (91%), H: D (91%), I: D (91%), K: D (91%), L: D (91%), M: D (91%), N: D (80%), P: D (91%), Q: D (85%), R: D (91%), S: D (85%), T: D (85%), V: D (91%), W: D (91%), Y: D (91%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Clinical, angiographic, and genetic factors associ... JAMA. 2011 Oct 26;306(16):1765-74. Cayla G, Hulot JS, O'Connor SA, Pathak A, Scott SA, Gruel Y, Silvain J, Vignalou JB, Huerre Y, de la Briolle A, Allanic F, Beygui F, Barthelemy O, Montalescot G, Collet JP
Clinical, angiographic, and genetic factors associated with early coronary stent thrombosis.
JAMA. 2011 Oct 26;306(16):1765-74., [PMID:22028352]
Abstract [show]
CONTEXT: Despite dual antiplatelet therapy, stent thrombosis remains a devastating and unpredictable complication of percutaneous coronary intervention (PCI). OBJECTIVE: To perform a sequential analysis of clinical and genetic factors associated with definite early stent thrombosis. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOME MEASURE: Accuracy of early stent thrombosis prediction by 23 genetic variants. RESULTS: 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). CONCLUSIONS: 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.
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61 The following variables were considered for inclusion in the comprehensive model: baseline demographic (age, sex, body mass index, smoking, and ancestry), clinical (hypertension, diabetes mellitus, previous myocar- dialinfarction,creatinineclearance Ͻ60 mL/min, left ventricular ejection fraction Ͻ40%, clopidogrel loading dose, and use of proton pump inhibitors [PPIs] and calcium channel blockers), and angiographic (American College of Cardiology/American Heart Association [ACC/AHA] type C lesion, number of vessels with disease, minimum stent diameter, acuteness of PCI, and post-PCI dissection) characteristics; predicted metabolic status (CYP2C19, CYP2C9, and CYP2B6); and genetic variants (CYP3A5*3, POR*28, PON1 Q192R and L55M, ABCB1 C3435T, P2Y12 H1/H2, ITGB3 T1565C, MTHFR C677T, PAI1 5G/ 4G, factor V G1691A, prothrombin G20210A, fibrinogen G455A, and VKORC1).
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ABCB1 p.Gly455Ala 22028352:61:865
status: NEW