RESUMEN
INTRODUCTION AND OBJECTIVES: We examined whether the rs180070 and rs2070011 polymorphisms of the fibrinogen gene could affect the risk of coronary artery disease in hypertensive patients by modifying the inflammatory process and coagulation. METHODS: A total of 744 participants underwent coronary angiography due to symptoms of stable angina, while hypertension was present in 332 patients. RESULTS: The presence of the A allele (rs180070) was associated with significantly high levels of fibrinogen in hypertensive patients (P=.05). On multivariate analysis, A homozygosity (rs180070) (ß = 0.257 ± 18.6; P<.001), but not hypertension status (ß = 0.05 ± 11.9; P=.29) was an independent predictor of fibrinogen levels. In hypertensive patients, higher fibrinogen levels>443mg/dL (odds ratio = 3.50; 95% confidence interval, 1.14-10.90; P=.029), but not A homozygosity (odds ratio = 3.00; 95% confidence interval, 0.78-11.90; P = .110) were independent predictors of the presence of coronary artery disease. Moreover, interleukin-6 levels were higher in A homozygotes for the rs180070 polymorphism compared with all other genotypes (P=.046). Indeed, this genotype was the only adjusted independent predictor of interleukin-6 levels (ß = 0.151 ± 0.642; P=.032). It was also associated with higher D-dimer levels in hypertension compared with G allele carriers (P=.048). CONCLUSIONS: The presence of A homozygosity (rs180070) is associated with increased levels of inflammatory mediators and a higher incidence of angiographic coronary artery disease. Importantly, fibrinogen is an independent predictor of the angiographic presence of coronary artery disease in hypertensive patients.
Asunto(s)
Aterosclerosis/genética , Enfermedad de la Arteria Coronaria/genética , Vasos Coronarios/diagnóstico por imagen , ADN/genética , Fibrinógeno/genética , Hipertensión/complicaciones , Polimorfismo Genético , Alelos , Aterosclerosis/sangre , Aterosclerosis/complicaciones , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/complicaciones , Femenino , Fibrinógeno/metabolismo , Variación Genética , Genotipo , Humanos , Hipertensión/sangre , Hipertensión/genética , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Factores de RiesgoRESUMEN
BACKGROUND: Fibrinogen is a coagulation/inflammatory biomarker strongly associated with atherogenesis. Data have reported that the genetic variability on fibrinogen chains may affect the atherosclerotic process and the risk of coronary artery disease (CAD). We examined the combined effects of the G455A and the G58A fibrinogen genetic polymorphisms on prothrombotic profile, endothelial function and the risk of CAD in a Caucasian population. METHODS: We recruited 422 patients with angiographically documented CAD and 277 controls matched for age and gender. The two polymorphisms were genotyped by polymerase chain reaction and restriction endonuclease digestion. Fibrinogen and D-Dimers levels, as well as factors' (f) V, X activity were measured by standard coagulometry techniques. Endothelial function was assessed by the flow mediated dilatation (FMD) of the brachial artery. RESULTS: The two polymorphisms had no significant effect on the risk for CAD. Although the 58AA subjects had not significantly different levels of fibrinogen compared with the 58GG+GA in both groups (p=NS), we importantly found that the 455AA homozygosity was associated with increased fibrinogen levels not only in the control group (p=0.035), but also in the CAD group (p<0.001) compared to the G allele carriers. Moreover, both the 58AA (p=0.016) and 455AA homozygotes (p=0.022) presented with higher levels of D-Dimers in the CAD group. Interestingly, the 455AA homozygotes had increased fV activity in the CAD group (p=0.048). However, no significant effects were observed on fX activity and FMD. CONCLUSIONS: Both fibrinogen polymorphisms are capable to modify the atherosclerotic process via their effects on the coagulation cascade.