title: Association of the single nucleotide polymorphism rs599839 in the vicinity of the sortilin 1 gene with LDL and triglyceride metabolism, coronary heart disease and myocardial infarction. The Ludwigshafen Risk and Cardiovascular Health Study.
abstract: OBJECTIVE
  The rs599839 polymorphism A/G in the vicinity of the sortilin 1 gene has been reported to be associated with low density lipoprotein cholesterol (LDL-C) and coronary artery disease (CAD). The objective of this study was to further characterize the protective effect of the minor allele by analyzing the association with a variety of quantitative traits.
  
  
  METHODS
  Association of rs599839 with plasma levels of different parameters of LDL and triglyceride (TRIG) metabolism as well as the risk of CAD was tested in the LURIC study cohort.
  
  
  RESULTS
  Compared to AA homozygotes, the levels of LDL-C, low density lipoprotein triglycerides (LDL-TRIG) and apolipoprotein B were decreased in carriers of at least one G-allele. The G-allele was also associated with an increasing radius of the LDL particles. Regarding TRIG metabolism we observed a significant decrease in the level of triglycerides for homozygous carriers of the G-allele as well as decreased levels of free fatty acids (FFA), free glycerol and free cholesterol. With each G-allele the prevalence of CAD (multivariate OR 0.806; 95% CI: 0.692-0.940, P=0.006) decreased significantly whereas we observed only a marginal decrease for MI which did not reach significance. For GG homozygotes, the OR for CAD was 0.588 (95% CI: 0.394-0.877; P=0.009) and the OR for previous myocardial infarction (MI) was 0.693 (95% CI: 0.490-0.980; P=0.038). These associations were independent of cardiovascular risk factors.
  
  
  CONCLUSIONS
  In the LURIC Study the G-allele of rs599839 is associated with LDL and TRIG metabolism and the risk of coronary artery disease and myocardial infarction.
authors.affiliation: LURIC Study Nonprofit LLC, Freiburg, Germany.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.forename: Wilfried
authors.initials: W
authors.lastname: Renner
authors.forename: Tanja B
authors.initials: TB
authors.lastname: Grammer
authors.forename: Patrick
authors.initials: P
authors.lastname: Linsel-Nitschke
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Boehm
authors.forename: Bernhard R
authors.initials: BR
authors.lastname: Winkelmann
authors.forename: Peter
authors.initials: P
authors.lastname: Bugert
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hoffmann
authors.forename: Winfried
authors.initials: W
authors.lastname: März
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D008078:Cholesterol, LDL / Q000097:blood*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003327:Coronary Disease / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood*; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D000099183:Sortilin; C032607:low density lipoprotein triglyceride