A Common Variant at Chromosome 9P21.3 Is Associated With Age of Onset of Coronary Disease but Not Subsequent Mortality

Abstract

Background— Chromosome 9p21.3 (chr9p21.3) recently was identified by several genome-wide association studies as the genomic region most strongly associated with the risk of coronary artery disease. Within the chr9p21.3 locus, the single-nucleotide polymorphism rs1333049 has been demonstrated to be most strongly associated with susceptibility to developing coronary artery disease. However, the effect of rs1333049 on clinical outcomes in patients with established coronary disease has yet to be determined. Methods and Results— Coronary Disease Cohort Study (CDCS) (n=1054) and Post-Myocardial Infarction (PMI) (n=816) study participants were genotyped for rs1333049. Clinical history, circulating lipids, neurohormones, cardiac function, and discharge medications were documented. All-cause mortality and cardiovascular hospital readmissions were recorded over a median follow-up period of 4.0 years for the CDCS cohort and 9.1 years for the PMI cohort. The CDCS patients homozygous for the high-risk C allele had an age of onset 2 to 5 years earlier for coronary disease ( P =.005), angina ( P =.025), myocardial infarction ( P =.022), and percutaneous transluminal coronary angioplasty ( P =.009). Patients with the CC genotype also had higher levels of total cholesterol ( P =.033) and triglycerides ( P =.003). The PMI participants with the CC genotype were 3 years younger on admission ( P =.009). Cox proportional hazards analysis adjusting for established predictors of increased risk showed no significant association between rs1333049 genotype and mortality in either the CDCS ( P =.214) or the PMI ( P =.696) cohorts. Conclusions— The chr9p21.3 polymorphism rs1333049 was associated with an earlier age of disease onset in 2 coronary disease cohorts but not with poorer clinical outcome in either cohort.

Complex Evaluation of the Significance of Populational Genetic Markers Associated With Myocardial Infarction and Risk Factors

“…Ассоциа-ция с ИБС была показана для rs1333049 в исследова-нии в США и Португалии, где СС генотип полимор-физма rs1333049 был ассоциирован с повышенным риском ИБС [12][13][14]. Кроме того, носители СС гено-типа имели повышенный уровень триглицеридов и холестерина в крови [15]. По данным Ellis, et al (2010) этот ОНП ассоциирован с ранним началом ИБС.…”

“…По данным Ellis, et al (2010) этот ОНП ассоциирован с ранним началом ИБС. А согласно результатам, полученным Buysschaert, et al (2010) еще и с повторным ИМ и сер-дечной смертью после острого коронарного син-дрома [15,16].…”

Genomic Risk Variants at 1p13.3, 1q41, and 3q22.3 Are Associated With Subsequent Cardiovascular Outcomes in Healthy Controls and in Established Coronary Artery Disease

“…Previously, we have reported that a common risk variant within the 9p21.3 risk region was associated with age of CAD onset but not subsequent mortality. 16 In the current study, we have investigated the association between risk variants at 1p13.3, 1q41, and 3q22.3 and cardiovascular outcomes in both individuals free of overt cardiovascular disease (CVD) at the time of recruitment and in patients with established CAD.…”

The Relationship Between Polymorphisms on Chromosome 9p21 and Age of Onset of Coronary Heart Disease in Black and White Women

“…Previous research with whites, homozygous for the risk allele for rs1333049 compared to those with wild-type alleles, demonstrated a 2-5 years earlier onset of CHD (Ellis et al, 2010) and a strong association with 3-vessel disease in those with early onset CHD (Dondona et al, 2010). This supported previous findings that other SNPs in the same haplotype block (rs10757274, rs2383206, rs2383207, and rs10757278) were associated with premature CHD in whites (Helgadottir et al, 2007;Abdullah et al, 2008).…”

“…Studies differ in the selection of 9p21 SNPs and the definitions of early-onset disease but uniformly include few women or non-white populations. Chromosome 9p21 SNPs were correlated with early onset CHD in several white (Helgadottir et al, 2007;Abdullah et al, 2008;Meng et al, 2008;Ellis et al, 2010) and Chinese (Chen et al, 2009) populations but not in others (Broadbent et al, 2008;Dehghan et al, 2008). Approximately 25% of whites carry two copies of the 9p21 risk alleles with an estimated risk of early onset CHD that is twice that among individuals without these alleles (McPherson, 2010).…”