Abstract 17451: Dense Genotyping of Candidate Gene Loci Identifies Variants Associated with Oxidized Ldl Serum Levels
Background: Oxidized low-density lipoprotein (oxLDL) as a marker of oxidative stress has been proposed to play an important role in the development of atherosclerosis. OxLDL consists of a number of heterogeneously modified particles, including apoB, phospholipids, LDL-cholesterol, and unsaturated fatty acids. Serum levels of oxLDL are known to be heritable, but the degree of heritability has not been established yet.
Methods: We used a high-density genotyping array containing single-nucleotide polymorphisms (SNPs) from oxLDL candidate genes selected on known biology of oxLDL metabolism, mouse genetic studies, and human genetic association studies. SNP selection was based on tagging SNPs and included low-frequency nonsynonymous SNPs. 1,332 men and women from a randomly drawn subsample of the baseline examination of the MONICA/KORA Augsburg Cohort Study, conducted between 1984 and 1995, with measurements of oxLDL (Mercodia assay) and genotyping by the 50K IBC Chip comprised the study population. Linear regression analysis with adjustment for age, sex and survey was applied to assess the associations between gene variants and oxLDL levels. Statistical significance was defined as 5.0e-6 accounting for multiple testing.
Results: Eight SNPs showed a statistically significant association with ox-LDL and were located at chromosome 2 in the APOB gene with rs676210 having the strongest association (p value = 4.13e-12). All eight SNPs had minor allele frequencies above 20% showing a substantial gene variation.
Conclusions: In summary, we identified variants in the APOB gene that are associated with levels of oxLDL in the general population. These findings may not only enhance our understanding of oxidative pathways and lipid metabolism and function, but may also pave the way for novel research avenues.
- © 2011 by American Heart Association, Inc.