Genetic variation in fibrillin-1 gene is not associated with arterial stiffness in apparently healthy individuals

Abstract

Arterial stiffness is an independent determinant of cardiovascular risk, and there is evidence that it has a strong genetic component. Fibrillin-1 (FBN-1) is the disease gene for Marfan's syndrome and an FBN-1 polymorphism has been associated with large artery stiffening and elevated pulse pressure (PP) in patients with cardiovascular disease. The aim of this study was to investigate the possible influence of the common FBN-1 genotypes on arterial stiffness in a large cohort of healthy individuals. A total of 742 individuals free from cardiovascular disease or risk factors were studied. Aortic pulse wave velocity (PWV) and augmentation index (AIx), blood pressure, lipids and glucose were assessed. Genomic DNA was extracted, and genotyping for the FBN-1 variable nucleotide tandem repeat (VNTR) was performed using a CEQ 8000 sequencer. The mean age (+/- SEM) of the cohort was 49 +/- 1 years. The three common VNTR genotypes accounted for 87.1% of the population frequency. Their frequencies were: 52.3%, 2-2; 16.3%, 2-3; 18.5% 2-4. There were no significant differences in the blood pressure, AIx, PWV, lipids or body mass index among the common genotypes. Moreover, the FBN-1 genotype was not associated with either aortic PWV or other measures of stiffness after correction for other confounding factors. These data do not support the hypothesis that aortic PWV or PP are influenced by the FBN-1 VNTR genotype. Although we cannot exclude small effects, this negative finding also suggests that there is not a major allele for stiffness or blood pressure in apparently healthy individuals linked to this VNTR.