RGD Reference Report - Risk loci for coronary artery calcification replicated at 9p21 and 6q24 in the Heinz Nixdorf Recall Study. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Risk loci for coronary artery calcification replicated at 9p21 and 6q24 in the Heinz Nixdorf Recall Study.

Authors: Pechlivanis, S  Muhleisen, TW  Mohlenkamp, S  Schadendorf, D  Erbel, R  Jockel, KH  Hoffmann, P  Nothen, MM  Scherag, A  Moebus, S   
Citation: Pechlivanis S, etal., BMC Med Genet. 2013 Feb 8;14:23. doi: 10.1186/1471-2350-14-23.
RGD ID: 11058683
Pubmed: PMID:23394302   (View Abstract at PubMed)
PMCID: PMC3583714   (View Article at PubMed Central)
DOI: DOI:10.1186/1471-2350-14-23   (Journal Full-text)

BACKGROUND: Atherosclerosis is the primary cause of coronary heart disease (CHD), preceding the onset of cardiovascular disease by decades in most cases. Here we examine the association between single nucleotide polymorphisms (SNPs) integrated on Metabochip and coronary artery calcification (CAC), a valid risk factor for CHD, in an unselected, population-based German cohort. METHODS: The Metabochip is a custom iSELECT array containing >195,000 SNPs that was designed to support large-scale follow-up of putative associations for metabolic and cardiovascular-associated traits. We used generalized linear regression models to explore the impact of Metabochip SNPs on quantitative CAC in 4,329 participants. RESULTS: The 9p21 variant, rs1537373, was most strongly associated (Beta=0.30; 95% confidence interval (CI)=0.21-0.39; p=4.05x10-11) with quantitative CAC. The second strongest association with CAC was with rs9349379 in the phosphatase and actin regulator 1 gene, PHACTR1, (Beta=0.30; 95% CI=0.22-0.40; p=4.67x10-11). Both SNPs remained nominally significant in dichotomized analyses for the presence of any CAC (odds ratiors1537373 (OR)=1.19; 95% CI=1.07-1.31; p=0.001 and ORrs9349379=1.26; 95% CI=1.14-1.40); p=1.5x10-5). Fine mapping of the 9p21 and PHACTR1 gene region revealed several other SNPs that were strongly associated with CAC. CONCLUSION: We demonstrate that SNPs near 9p21 and in PHACTR1 that have previously been shown to be associated with CHD are strongly associated with CAC in the Heinz Nixdorf Recall Study cohort. Our findings suggest that the 9p21 and 6q24 loci might be involved in cardiac outcome via promoting development of atherosclerosis in the coronary arteries.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
PHACTR1HumanCoronary Artery Calcification  IAGP DNA:SNP:intron:g.13011943A>G (rs9349379) (human)RGD 
Phactr1RatCoronary Artery Calcification  ISOPHACTR1 (Homo sapiens)DNA:SNP:intron:g.13011943A>G (rs9349379) (human)RGD 
Phactr1MouseCoronary Artery Calcification  ISOPHACTR1 (Homo sapiens)DNA:SNP:intron:g.13011943A>G (rs9349379) (human)RGD 

Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
PHACTR1HumanCoronary artery calcification  IAGP DNA:SNP:intron:g.13011943A>G (rs9349379)RGD 

Genes (Rattus norvegicus)
Phactr1  (phosphatase and actin regulator 1)

Genes (Mus musculus)
Phactr1  (phosphatase and actin regulator 1)

Genes (Homo sapiens)
PHACTR1  (phosphatase and actin regulator 1)