- Title
- A common variant in low-density lipoprotein receptor-related protein 6 gene (LRP6) is associated with LDL-Cholesterol
- Creator
- Tomaszewski, Maciej; Charchar, Fadi; Barnes, Timothy; Gawron-Kiszka, Magdalena; Sedkowska, Agnieszka; Podolecka, Ewa; Kowalczyk, Jacek; Rathbone, Wendy; Kalarus, Zbigniew; Grzeszczak, Wladyslaw; Goodall, Alison; Samani, Nilesh; Zukowska-Szczechowska, Ewa
- Date
- 2009
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/32183
- Identifier
- vital:2136
- Identifier
-
https://doi.org/10.1161/atvbaha.109.185355
- Identifier
- ISSN:1079-5642
- 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. (Arterioscler Thromb Vasc Biol. 2009;29:1316-1321.)
- Relation
- Arteriosclerosis Thrombosis and Vascular Biology Vol. 29, no. 9 (2009), p. 1316-1321
- Rights
- Copyright American Heart Association
- Rights
- This metadata is freely available under a CCO license
- Subject
- Genes; Genetics; LDL-cholesterol; Lipids; Association
- Reviewed
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