Affiliation: Gillings School of Global Public Health, Department of Nutrition
Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous elements in the arteries. In mice, the aortic arch and root show distinct patterns of lesion development. A quantitative trait locus (QTL) analysis of an intercross between apoE-null mice on 129S6 and DBA/2J backgrounds has revealed a significant locus on chromosome 10, Aath5, that affects plaque size in the arch. One candidate gene in the Aath5 locus is the Stab2 gene, which encodes a receptor for hyaluronan. The DBA allele of the Stab2 gene includes a unique intracisternal A-particle (IAP) retrotransposon inserted in reverse in the promoter region, which drives Stab2 expression. Methylation status of this region was analyzed through allele-specific bisulfite sequencing and correlated with ectopic Stab2 expression in the heart and kidneys. Thus, epigenetic regulation of this IAP element may play a role in regulating Stab2 expression and affect atherosclerotic susceptibility in the aortic arch.