Lack of association of two common polymorphisms on 9p21 with risk of coronary heart disease and myocardial infarction; results from a prospective cohort study

The Rotterdam Study is a population-based, prospective cohort study among 7983 participants aged 55 years and older. Associations of the polymorphisms with CHD and MI were assessed by use of Cox proportional hazards analyses.In an additive model, the age and sex adjusted hazard ratios (HRs) (95% confidence interval) for CHD and MI were 1.03 (0.90, 1.18) and 0.94 (0.82, 1.08) per copy of the G allele of rs10757274. The corresponding HRs were 1.03 (0.90, 1.18) and 0.93 (0.81, 1.06) for the G allele of rs10757278. The association of the SNPs with CHD and MI was not significant in any of the subgroups of CHD risk factors.we were not able to show an association of the studied SNPs with risks of CHD and MI. This may be due to differences in genes involved in the occurrence of CHD in young and older people.It has been considered for long that genes play a substantial role in susceptibility to coronary heart disease (CHD) [1]. Up to now, a limited number of these genes have been identified through the candidate gene approach and genome wide linkage studies. Recently a number of genome wide association (GWA) studies have identified several genetic variants on chromosome 9p21 associated with the risk of CHD. McPherson et al. found a Single Nucleotide Polymorphism (SNP), rs10757274, on chromosome 9p21 associated with the risk of CHD [2]. Helgadottir et al. found a close-by SNP, rs10757278, in the same 9p21 region associated with the risk of myocardial infarction (MI) [3]. These findings were followed by another GWA study by Samani et al [4], which found rs1333049 to be associated with the risk of coronary artery disease [4]. All three SNPs are located within the same Linkage Disequilibrium (LD) block on chromosome 9 approximately 22 million base pairs from the 9p telomere, adjacent to two tumor suppressor genes, CDKN2A and CDKN2B. These genes are involved in regulation of cell proliferation. Abnormal proliferation is one of the characteristics of atherosclerosis, one of the pa