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


Aschauer, S; Mittermayer, F; Wagner, C C; Schmidt, W M; Brunner, M; Haslacher, H; Wolzt, M; Müller, M (2010). Forearm vasodilator reactivity in homozygous carriers of the 9p21.3 rs1333049 G>C polymorphism. European Journal of Clinical Investigation, 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.

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.

Citations

4 citations in Web of Science®
4 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic and Policlinic for Internal Medicine
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2010
Deposited On:01 Feb 2011 13:59
Last Modified:05 Apr 2016 14:41
Publisher:Wiley-Blackwell
ISSN:0014-2972
Publisher DOI:https://doi.org/10.1111/j.1365-2362.2010.02321.x
PubMed ID:20649639

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