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.
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.
Kleber
Marcus E
ME
LURIC Study Nonprofit LLC, Freiburg, Germany.
Renner
Wilfried
W
Grammer
Tanja B
TB
Linsel-Nitschke
Patrick
P
Boehm
Bernhard O
BO
Winkelmann
Bernhard R
BR
Bugert
Peter
P
Hoffmann
Michael M
MM
März
Winfried
W
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
D033942:Adaptor Proteins, Vesicular Transport; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D000099183:Sortilin; C032607:low density lipoprotein triglyceride