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Background  Studies suggest that the 9p21-3 locus may influence susceptibility to myocardial infarction. We performed a systematic review and meta-analysis to assess whether this locus is associated with severity of coronary atherosclerosis and adverse clinical outcomes in those with known coronary disease.    Methods  Multiple electronic databases were searched from inception through August 2012. Studies examining 9p21-3 genotype in patients with known coronary artery disease were included. We extracted the association of the 9p21-3 locus with measures of severity of coronary atherosclerosis [number of diseased vessels, Gensini Score, Duke CAD Prognostic Index (DPI)], angiographic outcomes [change in minimum lumen diameter (∆MLD) and number of new lesions at follow-up], and key clinical outcomes (all-cause mortality, recurrent myocardial infarction and the need for coronary revascularization). Relative risks (RR) and weighted mean difference (WMD) were pooled using the random effects models.    Results  23 cohorts enrolling 16,860 participants were analyzed. There was no significant difference between HR and LR genotypes in terms of all-cause mortality, recurrent myocardial infarction or the frequency of coronary revascularization. HR genotype was associated with increased risk of triple vessel disease (RR = 1.34; 95% CI 1.08-1.65; P = 0.01) and increased baseline Gensini Score (WMD = 5.30; 95% CI 0.66-9.93; P = 0.03). However there was no association with DPI (WMD = 4.00; 95% CI 2.94-10.94; P = 0.26). HR genotype did not predict ∆MLD or number of new lesions at follow-up.    Conclusions  Patients of coronary atherosclerosis who carry the high risk genotype of the 9p21-3 allele may be more likely to have multi-vessel CAD. However the effect of this allele on CAD progression and disease specific clinical outcomes are not observed possibly due to diminishing genetic risk following dietary modification and therapy.

The association of 9p21-3 locus with coronary atherosclerosis: a systematic review and meta-analysis