Abstract 3602: Relation of Plasma Phytosterol Levels and Common Genetic Polymorphisms for NPC1L1 and ABCG5/G8 to Incident Coronary Heart Disease in Middle-Aged Men and Women in the Atherosclerosis Risk in Communities (ARIC) Study
Phytosterols (plant sterols) have been associated with premature atherosclerosis in individuals with the rare genetic disorder sitosterolemia, and clinical studies have shown conflicting results as to whether more modest elevations in phytosterol concentrations (or their ratios to cholesterol) are associated with coronary heart disease (CHD). To examine whether plasma phytosterol concentrations or polymorphisms in genes that regulate phytosterol levels are associated with development of incident CHD events independent of established major CHD risk factors, we measured plasma sitosterol and campesterol concentrations and genotyped 6 SNPs for NPC1L1 and 1 SNP for ABCG5/G8 in men and women in without clinical CHD at baseline in the Atherosclerosis Risk in Communities (ARIC) cohort, a biracial cohort of 15,792 adults from 4 U.S. communities.
Plasma phytosterols: Baseline concentrations of plasma sitosterol and campesterol were not significantly different between 662 incident CHD cases and 747 noncases in a cohort random sample of 820 subjects (Table⇓). After additional adjustment for smoking status, systolic blood pressure, LDL-C, HDL-C, and diabetes, neither levels or ratios of phytosterols to cholesterol were associated with risk for CHD in multivariables-adjusted proportional hazards regression models. Phytosterols concentrations and phytosterol-to-cholesterol ratios were inversely related to individual components and number of components of the metabolic syndrome; both levels and ratios decreased with increasing numbers of components of the metabolic syndrome.
Genetic polymorphisms: In addition, genotyping was performed in 13,866 individuals, and 3 of the SNPs for NPC1L1 and the SNP for ABCG5/G8 were associated with levels of phytosterols but were not associated with incident CHD. In summary, in middle-aged Americans, neither levels of phytosterols nor polymorphisms for NPC1L1 and ABCG5/G8 were associated with incident CHD.