Cardiologia Clínica e Experimental
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Abstrato

Association of Chromosome 9p21.3 with Disease Location, Including the Number of Diseased Vessels, but not with Greater Burden of Coronary Disease

Benjamin D. Horne, John F. Carlquist, Daniel J. Rader, Joseph B. Muhlestein, John A. Huntinghouse, Muredach P. Reilly and Jeffrey L. Anderson1,

Introduction: Single nucleotide polymorphisms (SNPs) at chromosome 9p21.3 do not influence myocardial infarction, but their role in coronary artery disease (CAD) progression, burden, and outcomes is controversial. This study evaluated whether rs1333049 impacts CAD burden.

Methods: Non-diabetic CAD patients enrolled in the Intermountain Heart Collaborative Study (N=1,757) were evaluated for association of rs1333049 with the Duke CAD Index (primary endpoint) and other CAD measures. Multivariable regression adjusted for potential confounders. Statistical significance of secondary endpoints was corrected for multiple comparisons.

Results: No association of rs1333049 with Duke CAD Index was found for 0, 1, and 2 C alleles: 42.4 ± 16.1, 44.0 ± 17.4, 47.4 ± 17.6, respectively (p-trend=0.12, adjusted p-trend=0.11). It also did not predict the number of CAD lesions (adjusted p-trend=0.11) or the maximum CAD stenosis (adjusted p-trend=0.89). The SNP did predict the number of major vessels with proximal or left main lesions (0.56 ± 0.69, 0.62 ± 0.74, and 0.71 ± 0.77 for 0, 1, and 2 C alleles, respectively; adjusted p-trend=0.0056) and another location parameter: the number of major vessels with at least one significant stenosis (p-trend=0.0017). Rs1333049 was not associated with future events, but association with CAD presence was confirmed (p-trend<0.0001).

Conclusion: Rs1333049 was not associated with CAD burden, lesion number or severity, or cardiovascular events. The SNP did strongly predict CAD presence and was associated with lesion location. These findings reaffirm that a primary role of 9p21.3 may be related to the presence of CAD rather than the clinical severity of obstructive lesions. Because follow-up angiography was not systematically performed, CAD progression could not be evaluated.