A Common Variant in Low-Density Lipoprotein Receptor-Related Protein 6 Gene (LRP6) Is Associated With LDL-Cholesterol

作者：Tomaszewski Maciej^*; Charchar Fadi J; Barnes Timothy; Gawron Kiszka Magdalena; Sedkowska Agnieszka; Podolecka Ewa; Kowalczyk Jacek; Rathbone Wendy; Kalarus Zbigniew; Grzeszczak Wladyslaw; Goodall Alison H; Samani Nilesh J; Zukowska Szczechowska Ewa

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2009, 29(9): 1316-1321.

DOI：10.1161/ATVBAHA.109.185355

• gene
• genetics
• LDL-cholesterol
• lipids
• association

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.)

• 出版日期2009-9