Association Between 9p21 Genomic Markers and Heart Disease

Abstract

REVENTING AND MANAGING CARdiovascular disease (CVD) presents a challenge for health care and public health. 1,2 Nonmodifiable risk factors include increasing age, male sex, and heredity. Modifiable risk factors include smoking, hypertension, dyslipidemia, obesity, physical inactivity, and diabetes. [3][4][5] Among men, the annual rate of initial CVD events increases from 3 to 74 per 1000 from ages 35 to 44 years to ages 85 to 94 years, respectively. Similar increases occur among women a decade later. 6 Biomarkers (eg, C-reactive protein) have been combined with traditional risk factors to predict CVD events, 7 and molecular markers hold further promise. In 2007, genome-wide association studies on CVD identified a series of associated singlenucleotide polymorphisms (SNPs) in an intergenic region of chromosome 9p21, near the CDKN2A (NM_000077) and CDKN2B (NM_004936) genes. 8,9 Currently, no comprehensive compilation of the 9p21 literature uses formal methods to estimate the strength of the association with heart disease (eg, effect size, heterogeneity, publication bias, credibility of cumulative evidence) and examine clinical utility. This analysis is part of a targeted systematic review on existing cardiogenomic panels that in-cluded 28 genes in addition to the 9p21 SNPs. That review was commissioned by the Evaluation of Genomic Applica-

A Replication Study and a Meta-Analysis of the Association between the CDKN2A rs1333049 Polymorphism and Coronary Heart Disease

“…There was no evidence showing that Since only one case-control study was identified in Africans, more well-designed genetic studies between rs1333049 and CHD in Africans are required. Compared with the previous meta-analyses of rs1333049 and CHD 23,27,28) , our meta-analysis included more datasets (18 more than Schunkert et al, 8 more than Palomaki et al and 13 more than Guo et al). Furthermore , we also excluded 2 stages that did not meet HWE in the controls.…”

The family history: the first genetic test, and still useful after all those years?

“…Naturally, the question was then posed as to the relative importance of this one marker in clinical risk prediction. In both a prospective cohort study of white women 49 and a meta-analysis of possible clinical utility, 50 knowledge of the 9p21 genotype added little or nothing to traditional risk factor assessment. The Evaluation of Genomic Applications in Practice and Prevention Working Group recently evaluated 9p21 and 57 other genetic variants linked by GWAS to coronary artery disease and "… found that the magnitude of net health benefit from use of any of these tests alone or in combination is negligible. "…”

MRAS gene marker rs9818870 is not associated with acute coronary syndrome in the Czech population and does not predict mortality in males after acute coronary syndrome

“…1.10-1.15, some publication bias must be expected since only positive results have been published so far. 13,20,[21][22][23] Four studies, with quite different designs, suggested a possible, but weak, association between the rs9818870 polymorphism at the MRAS locus and CVD risk. [8][9][10][11] In comparison with these studies, we failed to detect this polymorphism as a risk for ACS development in the Czech-Slavonic population.…”