TGF-β1 polymorphisms and arterial stiffness; the Rotterdam Study

Abstract

Arterial stiffness is a risk factor for cardiovascular disease. Transforming growth factor b1 is a pleiotropic cytokine, with many functions, including influence on the vascular wall (e.g., on angiogenesis, endothelial cells and the extracellular matrix). We investigated five functional polymorphisms in the transforming growth factor b1 gene (À800 G/A, À509 C/T, codon 10 Leu/Pro, codon 25 Arg/Pro and codon 263 Thr/Ile) in relation to arterial stiffness in a population-based study. A total of 3863 participants of the Rotterdam Study, a prospective population-based study, were included in the current study. The relations of the genotypes and haplotypes with arterial stiffness (pulse wave velocity (PWV), distensibility coefficient (DC) and pulse pressure (PP)) were studied using analyses of variance and linear regression. The analyses were adjusted for age, sex, mean arterial pressure, heart rate, conventional cardiovascular risk factors and measures of atherosclerosis. There were no associations between PWV and À800 G/A (P ¼ 0.56), À509 C/T (P ¼ 0.29), codon 10 (P ¼ 0.98) and, codon 25 (P ¼ 0.28). These polymorphisms were not associated with the DC or with PP. The haplotype-based analyses yielded similar results. The results of this study show that the TGF-b1 -800 G/A, À509 C/T, codon 10 Leu/Pro and codon 25 Arg/Pro polymorphisms are not associated with arterial stiffness.

Arterial stiffness in hypertensives in relation to expression of angiopoietin-1 and 2 genes in peripheral monocytes

“…In addition, we cannot rule out the possibility that the increase in Angs could be compensatory and their action protective, since there are indications from some studies that they may reduce target organ damage in a hypertensive animal model. 27 A previous study by Sie et al 28 was the first that attempted to find a relation between arterial stiffness and angiogenic factors, and more specifically transforming growth factor. The study was not able to show any significant correlation.…”

Association studies in current cardiovascular genetics – functional variants, tags or both?

“…10 None of these functional variants were associated with arterial stiffness, either in a single locus or haplotype analysis in the Rotterdam Study. 7 As such, this analysis adds to the list of many previous negative studies based on epidemiologically representative population samples, state-of-the-art methods of phenotyping and selection of the functional SNPs in the most relevant candidate genes.…”

“…11 From this point of view, the study by Sie et al 7 could be considered as another piece of evidence for a failure of candidate gene strategy based on stringent pathophysiological criteria.…”

“…The latter strategy was used by Sie et al 7 in their analysis of associations between arterial stiffness and transforming growth factor b1 gene (TGFB1) -one of the most important molecules in the pathogenesis of atherosclerosis. 8 Each of five TGFB1 SNPs genotyped in subjects from the Rotterdam Study, 7 has a functional potential to affect the ultimate bioavailability of the encoded protein.…”

“…8 Each of five TGFB1 SNPs genotyped in subjects from the Rotterdam Study, 7 has a functional potential to affect the ultimate bioavailability of the encoded protein.…”