Influence of fibrillin-1 genotype on the aortic stiffness in men

Abstract

Aortic stiffness is a predictor of cardiovascular mortality. The mechanical properties of the arterial wall depend on the connective tissue framework, with variation in fibrillin-1 and collagen I genes being associated with aortic stiffness and/or pulse pressure elevation. The aim of this study was to investigate whether variation in fibrillin-1 genotype was associated with aortic stiffness in men. The mechanical properties of the abdominal aorta of 79 healthy men (range 28-81 yr) were investigated by ultrasonographic phase-locked echo tracking. Fibrillin-1 genotype, characterized by the variable tandem repeat in intron 28, and collagen type I alpha 1 genotype characterized by the 2,064 G>T polymorphism, were determined by using DNA from peripheral blood cells. Three common fibrillin-1 genotypes, 2-2, 2-3, and 2-4, were observed in 50 (64%), 10 (13%), and 11 (14%) of the men, respectively. Those of 2-3 genotype had higher pressure strain elastic modulus and aortic stiffness compared with men of 2-2 or 2-4 genotype (P = 0.005). Pulse pressure also was increased in the 2-3 genotype (P = 0.04). There was no significant association between type 1 collagen genotype and aortic stiffness in this cohort. In conclusion, the fibrillin-1 2-3 genotype in men was associated with increased aortic stiffness and pulse pressure, indicative of an increased risk for cardiovascular disease.

Increased carotid plaque burden in men with the fibrillin‐1 2/3 genotype

“…8 The most common genotypes in the present and previous studies were 2/2, 2/3 and 2/4, accounting for 92.2% of the populations studied. [7][8][9][10]18,19 There was no association between FBN1 2/3 compared with the 2/2 and 2/4 genotypes and increased blood pressure in the present study, in accordance with findings from previous studies in health subjects. 10,18 However, a subsample of individuals in the study of Powell et al 18 with pulse pressure > 50 mmHg were found to have an association between the 2/3 genotype and pulse pressure, although there were only a few such subjects in the study.…”

“…Mutations in FBN1 cause Marfan syndrome, and mutated FBN1 has been associated with increased aortic stiffness as well as increases in central pulse pressure. 16,17 Several studies have investigated FBN1 genotypes in different populations, and the frequency of the genotypes in the present study is in accordance with what has been reported previously in healthy individuals, 9,10,18 patients with AAA 7,19 and patients with CAD. 8 The most common genotypes in the present and previous studies were 2/2, 2/3 and 2/4, accounting for 92.2% of the populations studied.…”

“…This adds further knowledge to earlier findings of increased blood pressures and aortic stiffness in men with the FBN1 2/3 genotype. 9 Arterial structure seems to have a genetic component that is independent of blood pressure and cardiovascular risk factors. Numerous studies have highlighted heritability to increased IMT.…”

“…This is in accordance with our earlier findings on apparently healthy firstdegree male relatives of AAA patients, whereby we found an association between the 2/3 genotype and increased heart rate, blood pressure and abdominal aortic stiffness. 9 Conversely, Yasmin et al 10 showed that the 2/3 genotype of the FBN1 gene was not associated with increased aortic pulse wave velocity (PWV) in apparently healthy individuals. Thus, the aims of the present population-based study were to investigate: (i) the cross-sectional association between the FBN1 2/3 genotype and traditional cardiovascular risk factors, carotid intima-media thickness (IMT) and the presence of plaque; and (ii) the association of the FBN1 2/3 genotype with the incidence of first cardiovascular events and all-cause mortality in middle-aged subjects.…”

Thoracic Aortic Aneurysm Frequency and Dissection Are Associated With Fibrillin-1 Fragment Concentrations in Circulation

“…6 Fibrillin-1 genotype has also been linked to TAA, dissection, and other aortic abnormalities in patients without Marfan syndrome. [7][8][9][10] Furthermore, a recent genome-wide association study identified a susceptibility locus for sporadic TAA and dissection in a region containing the fibrillin-1 gene. 11 Mutations in fibrillin-1 have been shown to destabilize fibrillin-1 protein, making it more susceptible to proteolytic degradation.…”