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Forearm vasodilator reactivity in homozygous carriers of the 9p21·3 rs1333049 G>C polymorphism
Author(s) -
Aschauer Stefan,
Mittermayer Friedrich,
Wagner Claudia C.,
Schmidt Wolfgang M.,
Brunner Martin,
Haslacher Helmuth,
Wolzt Michael,
Müller Markus
Publication year - 2010
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2010.02321.x
Subject(s) - genotype , single nucleotide polymorphism , allele , locus (genetics) , snp , coronary artery disease , medicine , vasodilation , forearm , genetics , cardiology , biology , pathology , gene
Eur J Clin Invest 2010; 40 (8): 700–705 Abstract 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.