Polymorphisms associated with cholesterol and risk of cardiovascular events
Polymorphisms associated with cholesterol and risk of cardiovascular events
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DOI：
10.1056/nejmoa0706728
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发表时间：
2008-03-20
影响因子：
158.5
通讯作者：
Orho-Melander, Marju
中科院分区：
文献类型：
--
作者：
Kathiresan, Sekar;Melander, Olle;Orho-Melander, Marju
背景资料：与血液低密度脂蛋白（LDL）或高密度脂蛋白（HDL）胆固醇相关的常见单核苷酸多态性（SNP）适度影响脂质水平。我们测试的假设，这种SNPs的组合有助于心血管疾病的风险。方法：我们研究了SNPs在9个位点的马尔莫饮食和癌症研究的心血管队列5414例。我们首先验证了SNP与LDL或HDL胆固醇之间的关联，随后根据不利等位基因的数量创建了基因型评分。我们使用考克斯比例风险模型，以确定第一次心血管事件的基因型score.Results的时间：所有9个单核苷酸多态性表现出复制与LDL或HDL胆固醇水平的关联。随着基因型得分的增加，LDL胆固醇水平从152 mg/dl增加到171 mg/dl（3.9至4.4 mmol/L），而HDL胆固醇从60 mg/dl下降到51 mg/dl（1.6至1.3 mmol/L）。在随访期间（中位数，10.6年），238例受试者首次发生心血管事件。在校正了包括基线血脂水平在内的协变量的模型中，基因型评分与心血管疾病的发生相关（P
Background: Common single-nucleotide polymorphisms (SNPs) that are associated with blood low-density lipoprotein (LDL) or high-density lipoprotein (HDL) cholesterol modestly affect lipid levels. We tested the hypothesis that a combination of such SNPs contributes to the risk of cardiovascular disease.Methods: We studied SNPs at nine loci in 5414 subjects from the cardiovascular cohort of the Malmo Diet and Cancer Study. We first validated the association between SNPs and either LDL or HDL cholesterol and subsequently created a genotype score on the basis of the number of unfavorable alleles. We used Cox proportional-hazards models to determine the time to the first cardiovascular event in relation to the genotype score.Results: All nine SNPs showed replication of an association with levels of either LDL or HDL cholesterol. With increasing genotype scores, the level of LDL cholesterol increased from 152 mg to 171 mg per deciliter (3.9 to 4.4 mmol per liter), whereas HDL cholesterol decreased from 60 mg to 51 mg per deciliter (1.6 to 1.3 mmol per liter). During follow-up (median, 10.6 years), 238 subjects had a first cardiovascular event. The genotype score was associated with incident cardiovascular disease in models adjusted for covariates including baseline lipid levels (P