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Comparative Study
. 2011 Mar 7:11:9.
doi: 10.1186/1471-2261-11-9.

Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry

Thomas Scheffold  1 , Silke Kullmann, Andreas Huge, Priska Binner, Hermann R Ochs, Wolfgang Schöls, Joachim Thale, Wolfgang Motz, Franz Josef Hegge, Christoph Stellbrink, Thomas Dorsel, Hartmut Gülker, Hubertus Heuer, Wilfried Dinh, Monika Stoll, Georg Haltern; Forschungsverbund Herz-Kreislauf in NRW (Research Consortium Heart and Circulation in North Rhine-Westphalia)
Affiliations
Comparative Study

Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry

Thomas Scheffold et al. BMC Cardiovasc Disord. .

Abstract

Background: Recent genome-wide association studies have identified several genetic loci linked to coronary artery disease (CAD) and myocardial infarction (MI). The 9p21.3 locus was verified by numerous replication studies to be the first common locus for CAD and MI. In the present study, we investigated whether six single nucleotide polymorphisms (SNP) rs1333049, rs1333040, rs10757274, rs2383206, rs10757278, and rs2383207 representing the 9p21.3 locus were associated with the incidence of an acute MI in patients with the main focus on the familial aggregation of the disease.

Methods: The overall cohort consisted of 976 unrelated male patients presenting with an acute coronary syndrome (ACS) with ST-elevated (STEMI) as well as non-ST-elevated myocardial infarction (NSTEMI). Genotyping data of the investigated SNPs were generated and statistically analyzed in comparison to previously published findings of matchable control cohorts.

Results: Statistical evaluation confirmed a highly significant association of all analyzed SNP's with the occurrence of MI (p<0.0001; OR: 1.621-2.039). When only MI patients with a positive family disposition were comprised in the analysis a much stronger association of the accordant risk alleles with incident disease was found with odds ratios up to 2.769.

Conclusions: The findings in the present study confirmed a strong association of the 9p21.3 locus with MI particularly in patients with a positive family history thereby, emphasizing the pathogenic relevance of this locus as a common genetic cardiovascular risk factor.

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Figures

Figure 1
Figure 1
Homozygous Odds Ratios and 95% Confidence Intervals for the investigated SNPs. Boxes indicate the relative size of samples. Grey boxes indicate ORs and CIs for the overall cohort of MI patients, black boxes for patients represented with a positive family history.
Figure 2
Figure 2
Haplotype analysis for the investigated SNPs. As can be seen, all SNPs with the exception of the rs1333040 show a positive association of the phenotype MI in the presents of a positive family history of the disease. The haplotypes GGGGC and AAAAG revealed the strongest association of MI with a positive family history.
See this image and copyright information in PMC

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