title: A common variant in low-density lipoprotein receptor-related protein 6 gene (LRP6) is associated with LDL-cholesterol.
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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Common polymorphism in the gene underlying monogenic form of coronary artery disease impacts on risk of LDL-C elevation.
authors: Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Wing, Glenfield Hospital, Leicester, LE3 9QP, UK. mt142@le.ac.uk
authors: Maciej
authors: M
authors: Tomaszewski
authors: Fadi J
authors: FJ
authors: Charchar
authors: Timothy
authors: T
authors: Barnes
authors: Magdalena
authors: M
authors: Gawron-Kiszka
authors: Agnieszka
authors: A
authors: Sedkowska
authors: Ewa
authors: E
authors: Podolecka
authors: Jacek
authors: J
authors: Kowalczyk
authors: Wendy
authors: W
authors: Rathbone
authors: Zbigniew
authors: Z
authors: Kalarus
authors: Wladyslaw
authors: W
authors: Grzeszczak
authors: Alison H
authors: AH
authors: Goodall
authors: Nilesh J
authors: NJ
authors: Samani
authors: Ewa
authors: E
authors: Zukowska-Szczechowska
mesh_terms: D000328:Adult; D008078:Cholesterol, LDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics*; D050171:Dyslipidemias / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000097:blood / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics*; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000097:blood; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D008078:Cholesterol, LDL; D026502:LDL-Receptor Related Proteins; C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D012333:RNA, Messenger