The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm.

deCODE Genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.
Nature Genetics (Impact Factor: 35.21). 03/2008; 40(2):217-24. DOI: 10.1038/ng.72
Source: PubMed

ABSTRACT Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Our aim was to evaluate the effect of SNPs in the 9p21 locus on genetic susceptibility of coronary heart disease in the East Asian population. We searched PubMed, EMBASE and CNKI for publications relating to the association between SNPs within the 9p21 locus and coronary heart disease in the East Asian population. This meta-analysis was assessed by STATA 9.2. Twenty-one studies from 15 eligible papers composing 25,945 cases and 31,777 control subjects were included in the meta-analysis. The odds ratio (OR) and 95% confidence interval (CI) for the risk allele was 1.30 (1.25-1.35) with moderate heterogeneity. No publication bias was observed in this study. Sensitivity analysis further strengthened the validity of this association. In conclusion, SNPs within the 9p21 locus were strongly associated with the risk of coronary heart disease in the East Asian population with a similar risk OR to the Caucasian population.
    Annals of Human Genetics 01/2013; · 2.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Stroke represents an enormous health problem worldwide. It describes a clinical syndrome which can be caused by a number of different pathologies, rather than a single disease. Over 80% of strokes are ischaemic, as opposed to haemorrhagic. This review covers advances in the genetics of both monogenic and multifactorial ischaemic stroke. Like many other complex diseases, progress in identifying genes for multifactorial stroke has been disappointing. However, genome-wide association study (GWAS) technology is starting to have a major impact on our understanding of the genetics of stroke. Early studies have shown that genetic associations identified with other diseases known to be associated with stroke, such as coronary heart disease and atrial fibrillation, are themselves genetic risk factors for stroke. A number of stroke GWASs are nearing completion; these have identified novel associations with ischaemic stroke. Most associations reported to date are with specific stroke subtypes. This parallels findings from monogenic causes of stroke where individual mutations usually predispose to specific stroke subtypes. This has implications for the understanding of the pathogenesis of stroke, and emphasizes the importance of careful stroke subtyping in genetic epidemiology studies. So far, studies have looked for genetic risk factors for stroke acting independently of environmental factors. However, we know that conventional environmental risk factors are important in stroke pathogenesis, and considerable evidence suggests that gene-environment interactions will be important. Identifying these is likely to require much larger sample sizes.
    Human Molecular Genetics 08/2011; 20(R2):R124-31. · 7.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Several studies have reported that polymorphisms on chromosome 9p21.3, near the CDKN2A/2B gene, are strongly associated with increased susceptibility to abdominal aortic aneurysm (AAA). However, no convincing data has been reported on a relationship between AAA and these variants in the Chinese Han population. The aim of this study was to evaluate the role of rs10757278 and rs1333049 in determining genetic susceptibility to AAA. A total of 155 AAA patients and 310 controls, comparable in age and gender, were enrolled in this study. DNA samples were genotyped for rs10757278 and rs1333049 using the MassArray system. The association between these two single nucleotide polymorphisms and AAAs was tested using multivariate logistic regression. Stratified analysis was also performed by clinical and laboratory features. Single nucleotide polymorphisms rs10757278 and rs1333049 were significantly associated with increased risk of AAA. The frequencies of rs10757278-G and rs1333049-C in AAA patients were significantly higher than in control subjects (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.11-2.11; P = .01, and OR, 1.48; 95% CI, 1.07-2.05; P = .02). Multiple logistic regression analysis indicated that, after adjusting for smoking habits, drinking habits, and histories of other chronic diseases, homozygosity of the risk allele for rs10758278-G and rs1333049-C also increased the likelihood of AAA (OR, 2.31; 95% CI, 1.22-4.36, and OR, 2.14; 95% CI, 1.13-4.05). The frequency of the GC haplotype was significantly higher in AAA patients than in control subjects (OR, 1.44; P = .038). Stratification analysis of clinical and laboratory features revealed no association between polymorphisms and aortic diameters in AAA patients. There was a significantly high frequency of the rs10757278 GG genotype in AAA patients with high serum total homocysteine compared with those control subjects with high serum total homocysteine (OR, 2.71; 95% CI, 1.12-6.58; P = .03) indicating that the genotype GG of rs10757278 might interact with the homocysteine biological pathway to stimulate the presence of AAA. Present data demonstrate that rs10757278 and rs1333049 on chromosome 9p21.3 are significantly associated with increased risk of AAA in the Chinese population and emphasize the need to further study the role of these markers in AAA.
    Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 12/2013; · 3.52 Impact Factor


Available from
May 28, 2014