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- Title
Forearm vasodilator reactivity in homozygous carriers of the 9p21·3 rs1333049 G>C polymorphism.
- Authors
Aschauer, Stefan; Mittermayer, Friedrich; Wagner, Claudia C.; Schmidt, Wolfgang M.; Brunner, Martin; Haslacher, Helmuth; Wolzt, Michael; Müller, Markus
- Abstract
Eur J Clin Invest 2010; 40 (8): 700–705 Aim Recently, a novel susceptibility locus for coronary artery disease (CAD) has been identified on chromosome 9p21·3, linked to the single-nucleotide polymorphism (SNP) rs1333049 G>C. However, the physiological mechanism through which this locus confers an increased CAD-risk is still unknown. The aim of the present case–control study was to test whether this chromosome 9p21·3 locus, represented by the rs1333049 variant, is associated with altered vasodilator resistance vessel function in healthy young volunteers. Design and results A total of 97 healthy male volunteers were screened for homozygous carriers of either the G- or the C-allele, the minor allele in European populations. Forearm blood flow (FBF) reactivity to acetylcholine (ACh) and glycerol trinitrate (GTN) was then studied in 10 C/C-genotype carriers compared with 10 control subjects harbouring the G/G-genotype. FBF responses to ACh and GTN were reduced in subjects homozygous for the C-allele of the rs1333049 SNP ( P < 0·05). FBF reactivity to the highest dose of ACh and GTN was 95% and 74% lower when compared with control subjects with the G/G-genotype. Conclusion Our study revealed a functional impairment in forearm artery vasodilator resistance in carriers of the rs1333049 C/C-genotype, thus providing evidence for a first physiological functional link underlying the genetic association of the 9p21·3 locus with an increased cardiovascular risk.
- Subjects
CORONARY disease; VASODILATORS; GENETIC polymorphisms; LOCUS (Genetics); HEMODYNAMICS
- Publication
European Journal of Clinical Investigation, 2010, Vol 40, Issue 8, p700
- ISSN
0014-2972
- Publication type
Article
- DOI
10.1111/j.1365-2362.2010.02321.x