9号染色体短臂21区与冠状动脉疾病相关的基因座及动脉粥样硬化的早期标志物
Coronary artery disease-associated locus on chromosome 9p21 and early markers of atherosclerosis.
作者信息
Samani Nilesh J, Raitakari Olli T, Sipilä Kalle, Tobin Martin D, Schunkert Heribert, Juonala Markus, Braund Peter S, Erdmann Jeanette, Viikari Jorma, Moilanen Leena, Taittonen Leena, Jula Antti, Jokinen Eero, Laitinen Tomi, Hutri-Kähönen Nina, Nieminen Markku S, Kesäniemi Y Antero, Hall Alistair S, Hulkkonen Janne, Kähönen Mika, Lehtimäki Terho
机构信息
Department of Cardiovascular Sciences, University of Leicester, UK.
出版信息
Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):1679-83. doi: 10.1161/ATVBAHA.108.170332. Epub 2008 Jul 3.
BACKGROUND
Genome-wide association studies have recently identified a locus on chromosome 9p21 that influences risk of coronary artery disease (CAD). The effect of the locus on early markers of atherosclerosis is unknown. We examined its association with carotid intima-media thickness (CIMT) and brachial flow-mediated dilatation (FMD).
METHODS AND RESULTS
We genotyped 2277 individuals, age 24 to 39 years, from the Cardiovascular Risk in Young Finns Study with CIMT and FMD measurements and 1295 individuals, age 46 to 76 years, from the Health 2000 Survey with CIMT for rs1333049, the chromosome 9p21 variant showing the strongest association with CAD. Both mean and maximum CIMT were significantly higher (P<0.001) in the older subjects of the Health 2000 Survey compared with the Young Finns Study. However, there was no association of the rs1333049 genotype with either mean or maximum CIMT at either age (P=0.959 and 0.977 for the 2 phenotypes in the Young Finns Study and P=0.714 and 0.725 in the Health 2000 Survey). Similarly, there was no association of the locus with variation in FMD in the Young Finns cohort (P=0.521).
CONCLUSIONS
The chromosome 9p21 locus does not influence CAD risk through a mechanism that also affects CIMT or induces early changes in FMD.
背景
全基因组关联研究最近在9号染色体p21区域发现了一个影响冠状动脉疾病（CAD）风险的基因座。该基因座对动脉粥样硬化早期标志物的影响尚不清楚。我们研究了其与颈动脉内膜中层厚度（CIMT）和肱动脉血流介导的血管舒张（FMD）的关联。
方法与结果
我们对来自年轻芬兰人心血管风险研究的2277名年龄在24至39岁之间的个体进行了基因分型，并测量了他们的CIMT和FMD；还对来自健康2000调查的1295名年龄在46至76岁之间的个体进行了CIMT测量，以检测与CAD关联最强的9号染色体p21变体rs1333049。与年轻芬兰人研究相比，健康2000调查中年龄较大的受试者的平均CIMT和最大CIMT均显著更高（P<0.001）。然而，rs1333049基因型在两个年龄组中与平均CIMT或最大CIMT均无关联（在年轻芬兰人研究中，两种表型的P值分别为0.959和0.977；在健康2000调查中，P值分别为0.714和0.725）。同样，在年轻芬兰人群体中，该基因座与FMD的变化也无关联（P=0.521）。
结论
9号染色体p21基因座不会通过影响CIMT或引起FMD早期变化的机制来影响CAD风险。
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