Companioni Osmel, Rodríguez Esparragón Francisco, Fernández-Aceituno Alfonso Medina, Rodríguez Pérez José Carlos
Unidad de Investigación, Hospital Universitario de Gran Canaria Dr. Negrín, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, España.
Rev Esp Cardiol. 2011 Jun;64(6):509-14. doi: 10.1016/j.recesp.2011.01.010. Epub 2011 May 6.
Genome-wide association studies have shown an association between single nucleotide polymorphisms (SNPs) and coronary artery disease and myocardial infarction in new chromosomal regions: 1p13.1, 2q36.3, 9p21 and 10q11.21. The SNPs from the 9p21 region constitute a risk haplotype due to the strong linkage disequilibrium in this area. These SNPs have been extensively replicated in several European and Asian populations, and are associated with other pathologies such as abdominal aortic and intracranial aneurysms, and with intermediate phenotypes such as arterial stiffness and coronary calcium. The risk haplotype of 9p21 is located in a region without annotated genes, near CDKN2A and CDKN2B, known tumor suppressor genes encoding for inhibitors of cell cycle kinases. In the remaining regions the SNPs are located in genes with known roles in atherosclerosis as well as others with new roles. It has been shown that the incorporation of genetic information in the form of SNPs slightly improves the prediction of long-term cardiovascular risk estimated by the Framingham function, allowing the reclassification of individuals into more precise categories. Gene expression studies have found that expression levels of CDKN2A/CDKN2B/ANRIL are co-regulated and associated with the risk haplotype and atherosclerosis severity.
全基因组关联研究表明，新的染色体区域（1p13.1、2q36.3、9p21和10q11.21）中的单核苷酸多态性（SNP）与冠状动脉疾病和心肌梗死之间存在关联。由于9p21区域存在强烈的连锁不平衡，该区域的SNP构成了一种风险单倍型。这些SNP在多个欧洲和亚洲人群中得到了广泛验证，并且与其他病理状况（如腹主动脉瘤和颅内动脉瘤）以及中间表型（如动脉僵硬度和冠状动脉钙化）相关。9p21的风险单倍型位于一个没有注释基因的区域，靠近CDKN2A和CDKN2B，这两个是已知的肿瘤抑制基因，编码细胞周期激酶抑制剂。在其余区域，SNP位于在动脉粥样硬化中具有已知作用的基因以及具有新作用的其他基因中。研究表明，以SNP形式纳入遗传信息可略微改善通过弗雷明汉函数估计的长期心血管风险预测，从而将个体重新分类为更精确的类别。基因表达研究发现，CDKN2A/CDKN2B/ANRIL的表达水平受到共同调节，并且与风险单倍型和动脉粥样硬化严重程度相关。
