A common variant in low-density lipoprotein receptor-related protein 6 gene (LRP6) is associated with LDL-cholesterol.
A common variant in low-density lipoprotein receptor-related protein 6 gene (LRP6) is associated with LDL-cholesterol.
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DOI：
10.1161/atvbaha.109.185355
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发表时间：
2009-09
期刊：
影响因子：
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通讯作者：
Zukowska-Szczechowska E
中科院分区：
文献类型：
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作者：
Tomaszewski M;Charchar FJ;Barnes T;Gawron-Kiszka M;Sedkowska A;Podolecka E;Kowalczyk J;Rathbone W;Kalarus Z;Grzeszczak W;Goodall AH;Samani NJ;Zukowska-Szczechowska E
低密度脂蛋白受体相关蛋白6基因（LRP 6）的一种罕见突变被确定为单基因型冠心病的主要分子缺陷。我们假设LRP 6的常见变异可能使受试者易患LDL-胆固醇（LDL-C）升高。对来自213个波兰家系（西里西亚心血管研究家族）的703名个体进行了LRP 6中12种常见（次要等位基因频率≥0.1）单核苷酸多态性的基因分型。基于家族的分析显示，rs 10845493的次要等位基因与后代中LDL-C升高聚集的频率高于偶然预期（p=0.0053）。仅限于未接受降脂治疗的受试者的定量分析证实了rs 10845493与家族以及2个额外人群（来自西里西亚心血管研究重复组的218例无关受试者和来自青年男性心血管协会队列的1138例个体）中年龄、性别和BMI校正的LDL-C循环水平之间的相关性（分别为p=0.0268、p=0.0476和p=0.0472）。在3个人群的逆方差加权荟萃分析中，rs 10845493的每个额外次要等位基因拷贝与年龄、性别和BMI校正的LDL-C增加0.14 mmol/L相关（SE=0.05，p=0.0038）。单基因型冠心病潜在基因的常见多态性影响LDL-C升高风险
A rare mutation in low density lipoprotein receptor-related protein 6 gene (LRP6) was identified as the primary molecular defect underlying monogenic form of coronary artery disease. We hypothesised that common variants in LRP6 could predispose subjects to elevated LDL-cholesterol (LDL-C). 12 common (minor allele frequency ≥0.1) single nucleotide polymorphisms in LRP6 were genotyped in 703 individuals from 213 Polish pedigrees (Silesian Cardiovascular Study families). The family-based analysis revealed that the minor allele of rs10845493 clustered with elevated LDL-C in offspring more frequently than expected by chance (p=0.0053). The quantitative analysis restricted to subjects free of lipid-lowering treatment confirmed the association between rs10845493 and age-, sex- and BMI-adjusted circulating levels of LDL-C in families as well as 2 additional populations - 218 unrelated subjects from Silesian Cardiovascular Study replication panel and 1138 individuals from Young Men Cardiovascular Association cohort (p=0.0268, p=0.0476 and p=0.0472, respectively). In the inverse variance weighted meta-analysis of the 3 populations each extra minor allele copy of rs10845493 was associated with 0.14 mmol/L increase in age-, sex- and BMI-adjusted LDL-C (SE=0.05, p=0.0038). Common polymorphism in the gene underlying monogenic form of coronary artery disease impacts on risk of LDL-C elevation.