BACKGROUND: Elevated pulse pressure is associated strongly with adverse cardiovascular outcome; however, the genetic basis of this condition is unknown. This study examined whether genotypic variation in the extracellular matrix protein @entity6099 , the Marfan gene, was associated with aortic stiffening and therefore could contribute to cardiovascular risk associated with pulse pressure elevation in @entity301 . METHODS AND RESULTS: @entity1 (n=145; 113 @entity1 ), 62+/-9 years of age (mean+/-SD), with angiographically confirmed @entity301 , were studied. Carotid applanation tonometry was used to assess central blood pressures, and in conjunction with Doppler velocimetry, to assess aortic input and characteristic impedance. @entity6099 genotype was characterized by a variable @entity377 tandem repeat and 2 single- @entity377 polymorphisms. The variable @entity377 tandem repeat was a good predictor of underlying haplotypes with 3 genotypes (2-2, 2-4, and 2-3) accounting for 86% of the population. The 2-3 genotype had higher input impedance (P=0.002), characteristic impedance (P=0.005), and carotid pulse pressure (P=0.002) compared with the 2-2 and 2-4 genotypes. Disease severity assessed by previous angioplasties and the number of @entity1 with a stenosis >90% was also greater in the 2-3 genotype. Furthermore, in a multivariate analysis, @entity6099 genotype and central pulse pressure were independent of conventional risk factors in determining @entity301 severity. There was no difference in age, sex ratio, body mass index, smoking status, @entity165 level, or medication among the 3 genotypes. CONCLUSIONS: Although a causative link has not been shown, these data are consistent with an important role for @entity6099 genotype in cardiovascular risk associated with large-artery stiffening and pulse pressure elevation in individuals with @entity301 .

@entity6099 genotype is associated with aortic stiffness and disease severity in XXXX with coronary artery disease.

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients', 'men'] @entity301 :: ('MESH:D003327', 'Disease') :: ['coronary disease'] @entity6099 :: ('2200', 'Gene') :: ['fibrillin-1', 'Fibrillin-1'] @entity377 :: ('CHEBI:36976', 'Chemical') :: ['nucleotide'] @entity165 :: ('MESH:D002784', 'Chemical') :: ['cholesterol']
@entity1 :: (9606,Species) :: ['patients']
