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Title: A Common Variant in Low-Density Lipoprotein Receptor–Related Protein 6 Gene (LRP6) Is Associated With LDL-Cholesterol
Authors: Charchar, F. J.
Barnes, T.
Gawron-Kiszka, M.
Sedkowska, A.
Podolecka, E.
Kowalczyk, J.
Rathbone, W.
Kalarus, Z.
Grzeszczak, W.
Goodall, A. H.
Samani, N. J.
Zukowska-Szczechowska, E.
First Published: Sep-2009
Publisher: American Heart Association
Citation: Zbigniew Kalarus, Wladyslaw Grzeszczak, Alison H. Goodall, Nilesh J. Samani and Agnieszka Sedkowska, Ewa Podolecka, Jacek Kowalczyk, Wendy Rathbone, Maciej Tomaszewski, Fadi J. Charchar, Timothy Barnes, Magdalena Gawron-Kiszka, Gene (LRP6) Is Associated With LDL-Cholesterol A Common Variant in Low-Density Lipoprotein Receptor Related Protein 6Arterioscler Thromb Vasc Biol 2009;29;1316-1321
Abstract: Objective: 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 hypothesized that common variants in LRP6 could predispose subjects to elevated LDL-cholesterol (LDL-C). Methods and Results: Twelve 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). Conclusions: Common polymorphism in the gene underlying monogenic form of coronary artery disease impacts on risk of LDL-C elevation. We have hypothesized that common alleles in the locus underlying monogenic form of coronary artery disease (low-density lipoprotein receptor-related protein 6 gene [LRP6]) are associated with LDL-cholesterol. Through genetic association analyses we identified a common variant (rs10845493) in LRP6 as a significant determinant of LDL-cholesterol.
DOI Link: 10.1161/ATVBAHA.109.185355
Type: Article
Description: This is the author’s final draft of the paper. The final published version is available at the DOI below:
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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