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A common variant in low-density lipoprotein receptor-related protein 6 gene (LRP6) is associated with LDL-cholesterol.


ABSTRACT: 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).Twelve common (minor allele frequency > or =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.

SUBMITTER: Tomaszewski M 

PROVIDER: S-EPMC2814817 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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A common variant in low-density lipoprotein receptor-related protein 6 gene (LRP6) is associated with LDL-cholesterol.

Tomaszewski Maciej M   Charchar Fadi J FJ   Barnes Timothy T   Gawron-Kiszka Magdalena M   Sedkowska Agnieszka A   Podolecka Ewa E   Kowalczyk Jacek J   Rathbone Wendy W   Kalarus Zbigniew Z   Grzeszczak Wladyslaw W   Goodall Alison H AH   Samani Nilesh J NJ   Zukowska-Szczechowska Ewa E  

Arteriosclerosis, thrombosis, and vascular biology 20090810 9


<h4>Objective</h4>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).<h4>Methods and results</h4>Twelve common (minor allele frequency > or =0.1) single nucleotide polymorphisms in LRP6 were genotyped in 703 individuals from 213 Polish pedigrees (Silesian Cardi  ...[more]

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