Genetic variation in ABCA1 predicts ischemic heart disease in the general population
Genetic variation in ABCA1 predicts ischemic heart disease in the general population
复制标题
DOI：
10.1161/atvbaha.107.153858
复制
发表时间：
2008-01-01
影响因子：
8.7
通讯作者：
Tybjaerg-Hansen, Anne
中科院分区：
文献类型：
--
作者：
Frikke-Schmidt, Ruth;Nordestgaard, Borge G.;Tybjaerg-Hansen, Anne
目的-我们测试的假设，6个非同义单核苷酸多态性（SNPs）在ATP结合盒转运蛋白A1（ABCA 1）影响缺血性心脏病（IHD）的风险在一般population.Methods和结果-我们基因分型9259人从丹麦一般人群，随后25年。两个SNP（V771 M和V825 I）先前与HDL-C升高相关，1个（R1587 K）与HDL-C降低相关，而3个（R219 K，I883 M和E1172 D）不影响HDL-C水平。尽管如此，6个SNPs中的5个（V771 M，V825 I，I883 M，E1172 D，R1587 K）预测IHD的风险增加。在932例IHD病例与7999例对照的验证样本中获得了类似的结果。逐步回归方法确定V771 M，I883 M，和E1172 D作为IHD的最重要的预测因子和IHD的风险的加性效应存在V771 M/I883 M和I883 M/E1172 D pairs.Conclusions -我们发现，3 ABCA 1的6个非同义SNPs预测IHD的风险在一般人群中。
Objective - We tested the hypothesis that 6 nonsynonymous single nucleotide polymorphisms ( SNPs) in ATP-Binding-Cassette transporter A1 (ABCA1) affect risk of ischemic heart disease (IHD) in the general population.Methods and Results - We genotyped 9259 individuals from the Danish general population followed for 25 years. Two SNPs (V771M and V825I) were previously associated with increases in HDL-C, 1 (R1587K) with decreased HDL-C, whereas 3 (R219K, I883M and E1172D) did not affect HDL-C levels. Despite this, 5 out of 6 SNPs ( V771M, V825I, I883M, E1172D, R1587K) predicted increased risk of IHD. Similar results were obtained in a verification sample with 932 IHD cases versus 7999 controls. A stepwise regression approach identified V771M, I883M, and E1172D as the most important predictors of IHD and additive effects on IHD risk were present for V771M/I883M and I883M/E1172D pairs.Conclusions - We show that 3 of 6 nonsynonymous SNPs in ABCA1 predict risk of IHD in the general population.