Forearm vasodilator reactivity in healthy male carriers of the 3q22.3 rs9818870 polymorphism.
BACKGROUND
A genome wide association study has identified a robust risk locus for cardiovascular disease on 3q22.3. However, the mechanisms by which the [C]/[T] polymorphism rs9818870 increases cardiovascular risk are unknown. This forearm blood flow (FBF) study addressed the question if the genetic association with cardiovascular disease in patients is preceded by incipient vasodilator impairment in young, healthy carriers of this new risk locus on chromosome 3.


METHODS
After a pre-screening of 74 subjects 17 male healthy volunteers homozygous/heterozygous for a single nucleotide polymorphism (SNP) risk allele on 3q22.3 and a control group of 17 healthy volunteers not carrying the allele were included into this case-control study.


RESULTS
Forearm vascular endothelium-dependent and -independent vasodilator responses were in the normal range in both groups, although endothelium-dependent FBF reactivity to acetylcholine was significantly higher in SNP carriers of the risk allele.


CONCLUSIONS
The augmented endothelium-dependent vasodilation of the forearm resistance vasculature does not support the presence of endothelial dysfunction in young SNP carriers and indicates that other mechanisms are responsible for the strong association between coronary artery diseases and the rs9818870 polymorphism, located on 3q22.3.
Department of Clinical Pharmacology, Medical University of Vienna, Austria.
Stefan
S
Aschauer
Department of Clinical Pharmacology, Medical University of Vienna, Austria.
Martin
M
Brunner
Department of Clinical Pharmacology, Medical University of Vienna, Austria.
Michael
M
Wolzt
Department of Laboratory Medicine, Medical University of Vienna, Austria.
Helmuth
H
Haslacher
Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Austria.
Robin
R
Ristl
Department of Clinical Pharmacology, Medical University of Vienna, Austria. Electronic address: markus.mueller@meduniwien.ac.at.
Markus
M
Müller
D000328:Adult; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D003324:Coronary Artery Disease / Q000235:genetics* / Q000503:physiopathology; D005542:Forearm / Q000098:blood supply; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014664:Vasodilation / Q000235:genetics*; D055815:Young Adult
Chromosome 3q22.3; Coronary artery disease; Forearm blood flow; Single nucleotide polymorphism; Vascular function