Limits...
Novel genetic variants linked to coronary artery disease by genome-wide association are not associated with carotid artery intima-media thickness or intermediate risk phenotypes.

Cunnington MS, Mayosi BM, Hall DH, Avery PJ, Farrall M, Vickers MA, Watkins H, Keavney B - Atherosclerosis (2008)

Bottom Line: No significant association was found between genotype at any SNP and CIMT in 846 individuals with acceptable measurements.Nor were SNPs significantly associated with blood pressure, obesity, cholesterol, CRP, interleukin-6, TNF-alpha, or leptin.These novel CAD variants are not associated with CIMT and do not appear to mediate the risk of atherothrombosis through known risk factors.

View Article: PubMed Central - PubMed

ABSTRACT

Background: It is uncertain whether the novel single nucleotide polymorphisms (SNPs) that have recently been associated with coronary artery disease (CAD) in genome-wide studies also influence carotid atheroma and stroke risk. The mechanisms of their association with CAD are unknown; relationships to other cardiovascular phenotypes may give mechanistic clues. Carotid artery intima-media thickness (CIMT) is a subclinical marker of atherosclerosis associated with stroke. We investigated association of reported CAD risk variants with CIMT, and with other intermediate phenotypes that may implicate causative pathways.

Methods: We studied 1425 members of 248 British Caucasian families ascertained through a hypertensive proband. We genotyped CAD risk SNPs on chromosomes 9 (rs1333049, rs7044859, rs496892, rs7865618), 6 (rs6922269) and 2 (rs2943634) using TaqMan. Merlin software was used for family-based association testing.

Results: No significant association was found between genotype at any SNP and CIMT in 846 individuals with acceptable measurements. Nor were SNPs significantly associated with blood pressure, obesity, cholesterol, CRP, interleukin-6, TNF-alpha, or leptin.

Conclusions: These novel CAD variants are not associated with CIMT and do not appear to mediate the risk of atherothrombosis through known risk factors.

Show MeSH

Related in: MedlinePlus

Linkage disequilibrium and minor allele frequencies of typed SNPs. Linkage disequilibrium plot for chromosome 9p21 SNPs showing in each diamond the D’ (on top) and r2 values (on bottom) for typed SNP combinations in our population. mAF = Minor allele frequency.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2654912&req=5

fig1: Linkage disequilibrium and minor allele frequencies of typed SNPs. Linkage disequilibrium plot for chromosome 9p21 SNPs showing in each diamond the D’ (on top) and r2 values (on bottom) for typed SNP combinations in our population. mAF = Minor allele frequency.

Mentions: Genotyping was complete for more than 95% of the 1393 participants with DNA available at all loci. Allele frequencies and linkage disequilibrium for typed SNPs are shown in Fig. 1; these were similar to the HapMap CEU population and did not deviate significantly from Hardy–Weinberg proportions.


Novel genetic variants linked to coronary artery disease by genome-wide association are not associated with carotid artery intima-media thickness or intermediate risk phenotypes.

Cunnington MS, Mayosi BM, Hall DH, Avery PJ, Farrall M, Vickers MA, Watkins H, Keavney B - Atherosclerosis (2008)

Linkage disequilibrium and minor allele frequencies of typed SNPs. Linkage disequilibrium plot for chromosome 9p21 SNPs showing in each diamond the D’ (on top) and r2 values (on bottom) for typed SNP combinations in our population. mAF = Minor allele frequency.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2654912&req=5

fig1: Linkage disequilibrium and minor allele frequencies of typed SNPs. Linkage disequilibrium plot for chromosome 9p21 SNPs showing in each diamond the D’ (on top) and r2 values (on bottom) for typed SNP combinations in our population. mAF = Minor allele frequency.
Mentions: Genotyping was complete for more than 95% of the 1393 participants with DNA available at all loci. Allele frequencies and linkage disequilibrium for typed SNPs are shown in Fig. 1; these were similar to the HapMap CEU population and did not deviate significantly from Hardy–Weinberg proportions.

Bottom Line: No significant association was found between genotype at any SNP and CIMT in 846 individuals with acceptable measurements.Nor were SNPs significantly associated with blood pressure, obesity, cholesterol, CRP, interleukin-6, TNF-alpha, or leptin.These novel CAD variants are not associated with CIMT and do not appear to mediate the risk of atherothrombosis through known risk factors.

View Article: PubMed Central - PubMed

ABSTRACT

Background: It is uncertain whether the novel single nucleotide polymorphisms (SNPs) that have recently been associated with coronary artery disease (CAD) in genome-wide studies also influence carotid atheroma and stroke risk. The mechanisms of their association with CAD are unknown; relationships to other cardiovascular phenotypes may give mechanistic clues. Carotid artery intima-media thickness (CIMT) is a subclinical marker of atherosclerosis associated with stroke. We investigated association of reported CAD risk variants with CIMT, and with other intermediate phenotypes that may implicate causative pathways.

Methods: We studied 1425 members of 248 British Caucasian families ascertained through a hypertensive proband. We genotyped CAD risk SNPs on chromosomes 9 (rs1333049, rs7044859, rs496892, rs7865618), 6 (rs6922269) and 2 (rs2943634) using TaqMan. Merlin software was used for family-based association testing.

Results: No significant association was found between genotype at any SNP and CIMT in 846 individuals with acceptable measurements. Nor were SNPs significantly associated with blood pressure, obesity, cholesterol, CRP, interleukin-6, TNF-alpha, or leptin.

Conclusions: These novel CAD variants are not associated with CIMT and do not appear to mediate the risk of atherothrombosis through known risk factors.

Show MeSH
Related in: MedlinePlus