Association of a sequence variant in DAB2IP with coronary heart disease.

Abstract

AIMS:

A sequence variant, rs7025486[A], in DAB2IP on chromosome 9q33 has recently been associated with coronary heart disease (CHD). We sought to replicate this finding and to investigate associations with a panel of inflammatory and haemostatic biomarkers. We also sought to examine whether this variant, in combination with a chromosome 9p21 CHD variant (rs10757278) and the Framingham risk score (FRS), could improve the prediction of events compared with the FRS alone.

METHODS AND RESULTS:

rs7025486 was genotyped in 1386 CHD cases and 3532 controls and was associated with CHD [odds ratio (OR) of 1.16, 95% confidence interval (CI) 1.05-1.29, P= 0.003]. Meta-analysis, using data from the original report and from genome-wide association studies in both the Wellcome Trust Case Control Consortium and the Cardiovascular Health Study, comprising 9968 cases and 20 048 controls, confirmed the association (OR of 1.10, 95% CI 1.06-1.14, P= 3.2 × 10(-6)). There was no association with a panel of CHD biomarkers, including any lipid, inflammation, or coagulation trait, nor with telomere length. Addition to the FRS of this variant plus rs10757278 on chromosome 9p21 improved the area under the receiver-operating characteristic curve (A(ROC)) from 0.61 to 0.64 (P= 0.03) as well as improving the reclassification (net reclassification index = 11.1%, P= 0.007).

CONCLUSION:

This study replicates a previous association of a variant in DAB2IP with CHD. Addition of multiple variants improves the performance of predictive models based upon classical cardiovascular risk factors.

• Authors: Seamus C Harrison, Jackie A Cooper, Kawah Li, Phillipa J Talmud, Reecha Sofat, Jeffery W Stephens, Anders Hamsten, HIFMECH Consortium, Julie Sanders, Hugh Montgomery, Andrew Neil, Simon Broome Research Consortium, Steve E Humphries
• Journal: European heart journal (Eur Heart J) Vol. 33 Issue 7 Pg. 881-8 (Apr 2012) ISSN: 1522-9645 [Electronic] England
• PMID: 21444365 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• DAB2IP protein, human
• ras GTPase-Activating Proteins

Topics

• Aged
• Case-Control Studies
• Chromosomes, Human, Pair 9 (genetics)
• Coronary Disease (genetics)
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Polymorphism, Single Nucleotide (genetics)
• Prospective Studies
• ROC Curve
• Risk Factors
• ras GTPase-Activating Proteins (genetics)