Sultan CS, Weitnauer M, Turinsky M, et al. - Given a thymine to cytosine transition (−1T>C) in the Kozak sequence of the CD40 gene (rs1883832) has been related to coronary heart disease (CHD) in an Asian population, recently, so researchers investigated whether the −1T>C single-nucleotide polymorphism (SNP) could confer risk for CHD in Caucasians by conducting an association study and determined its functional result in cultured endothelial cells (ECs). Genotype-stratified human EC characterization was done by using molecular and biochemical techniques and cell adhesion assays. Experts assessed SNP distribution among Caucasians in a hospital-based case–control CHD study, and via ELISA, they quantified serum levels of soluble CD40. They found baseline CD40 protein abundance on ECs was influenced by the SNP in the CD40 gene. In this study, the C allele of the CD40 SNP was shown to evoke a pro-inflammatory EC phenotype, compensated by an enhanced CD40 shedding to neutralize excess CD40 ligand. Homozygosity for the C allele was identified as the reason for a genetic vulnerability to atherosclerosis as well as its sequelae.