Subsets of SNPs define rare genotype classes that predict ischemic heart disease
Subsets of SNPs define rare genotype classes that predict ischemic heart disease
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DOI：
10.1007/s00439-006-0233-y
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发表时间：
2007-01-01
期刊：
影响因子：
5.3
通讯作者：
Tybjaerg-Hansen, Anne
中科院分区：
文献类型：
--
作者：
Frikke-Schmidt, Ruth;Sing, Charles F.;Tybjaerg-Hansen, Anne
假设单核苷酸多态性 (SNP) 可以解释一般人群中缺血性心脏病 (IHD) 的遗传倾向。缺乏证据证明这种变异的作用正在助长人们对遗传信息在医学实践中的应用的悲观情绪。在这项研究中，我们确定了载脂蛋白 E (APOE) 和脂蛋白脂肪酶 (LPL) 中的外显子和 5' SNP 在 24 年随访期间单独和组合预测普通人群中 8,456 名个体 IHD 发病率的效用。在男性中，除了吸烟、糖尿病和高血压之外，LPL D9N 还可以改善 IHD 的预测 (P = 0.03)。相对于最常见的基因型，罕见 D9N 变异杂合子和纯合子男性组的风险比 (HR) 为 1.69（95% 置信区间 = 1.10-2.58）。 APOE 中的 D9N 与 -219G > T 以及 LPL 中的 N291S 和 S447X 的成对组合显着改善了 IHD 的预测（分别为女性 P = 0.05，男性 P = 0.04，男性 P = 0.03），超越吸烟、糖尿病和高血压，并确定了具有 1.92-4.35 高度显着 HR 的个体亚组 (n = 6-94)。这些结果在病例对照研究 (n = 8,806) 中得到验证。总之，我们提供的证据表明，APOE 和 LPL 中的 SNP 组合可识别 IHD 风险显着增加的个体亚组，而与吸烟、糖尿病和高血压相关的风险除外。
Single nucleotide polymorphisms (SNPs) are hypothesized to explain the genetic predisposition to ischemic heart disease (IHD) in the general population. Lack of evidence for a role of such variation is fostering pessimism about the utility of genetic information in the practice of medicine. In this study we determined the utility of exonic and 5' SNPs in apolipoprotein E (APOE) and lipoprotein lipase (LPL) when considered singly and in combination for predicting incidence of IHD in 8,456 individuals from the general population during 24 years of follow-up. In men, LPL D9N improved prediction of IHD (P = 0.03) beyond smoking, diabetes and hypertension. The group of men heterozygous and homozygous for the rare D9N variant had a hazard ratio (HR) of 1.69 (95% confidence interval = 1.10-2.58) relative to the most common genotype. Pairwise combinations of D9N with -219G > T in APOE and N291S and S447X in LPL significantly improved the prediction of IHD (P = 0.05 in women, P = 0.04 in men, P = 0.03 in men, respectively) beyond smoking, diabetes and hypertension, and identified subgroups of individuals (n = 6-94) with highly significant HRs of 1.92-4.35. These results were validated in a case-control study (n = 8,806). In conclusion, we present evidence that combinations of SNPs in APOE and LPL identify subgroups of individuals at substantially increased risk of IHD beyond that associated with smoking, diabetes and hypertension.