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. CONCLUSION: 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. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
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. CONCLUSION: 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. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
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Authors: Jonathan M Kocarnik; Sarah A Pendergrass; Cara L Carty; James S Pankow; Fredrick R Schumacher; Iona Cheng; Peter Durda; José Luis Ambite; Ewa Deelman; Nancy R Cook; Simin Liu; Jean Wactawski-Wende; Carolyn Hutter; Kristin Brown-Gentry; Sarah Wilson; Lyle G Best; Nathan Pankratz; Ching-Ping Hong; Shelley A Cole; V Saroja Voruganti; Petra Bůžkova; Neal W Jorgensen; Nancy S Jenny; Lynne R Wilkens; Christopher A Haiman; Laurence N Kolonel; Andrea Lacroix; Kari North; Rebecca Jackson; Loic Le Marchand; Lucia A Hindorff; Dana C Crawford; Myron Gross; Ulrike Peters Journal: Circ Cardiovasc Genet Date: 2014-03-12