Forearm vasodilator reactivity in homozygous carriers of the 9p21.3 rs1333049 G>C polymorphism.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Aschauer
Stefan
S
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. stefan.aschauer@meduniwien.ac.at
Mittermayer
Friedrich
F
Wagner
Claudia C
CC
Schmidt
Wolfgang M
WM
Brunner
Martin
M
Haslacher
Helmuth
H
Wolzt
Michael
M
Müller
Markus
M
D000328:Adult; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005542:Forearm / Q000098:blood supply*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012039:Regional Blood Flow / Q000235:genetics; D014664:Vasodilation / Q000235:genetics*