Figure 6.

A genetic variant in COL15A1 is associated with atherosclerosis, leads to reduced COL15A1 gene expression in human aorta and its methylation state is correlated with disease. (A) Forty-two tag SNPs were selected to cover all of the known genetic variation in COL15A1. These SNPs were genotyped in an atherosclerosis sample (CATHGEN) and allelic association with atherosclerosis was assessed using multivariable logistic regression modeling adjusting for sex and known CAD risk factors. Significant (SNP38) and trending (SNP 41) SNPs are indicated with arrows. Underlined SmaI sites indicate sites that change DNA methylation with passage. (B) COL15A1 gene expression was assessed in aorta tissue regardless of disease and the data were grouped by genotype. C allele carriers have a significant reduction in COL15A1 gene expression. (C) The C allele of rs4142986 is the minor allele and creates a putative DNA methylation site in a region of the gene that changes methylation with age. DNA methylation at rs4142986 was measured in aorta samples scored for disease (Sudan IV). DNA Methylation (%) is plotted versus disease for individuals of each genotype. There is a significant correlation with disease and increased methylation. ^‡P, mixed model (see methods); †P, Pearson's correlation, two-tailed.