Association between RAGE variants and the susceptibility to atherosclerotic lesions in Chinese Han population

Receptor for advanced glycation end products (RAGE) is a major proinflammatory receptor and its role in atherosclerosis has only been emphasized recently. Increasing evidence has demonstrated an association between RAGE and the susceptibility to atherosclerosis development. Therefore, the role of RAGE in atherogenesis and the possible impact of genetic variations in RAGE on the atherosclerotic process in subjects with coronary artery disease (CAD) was investigated in the present study. The RAGE expression in carotid specimens was analyzed by immunohistochemistry and sequence variations of the RAGE gene selected from the Hapmap database were also screened. The plasma levels of S100 calcium binding protein B (S100B) were determined by ELISA. Immunohistochemical staining of tissue samples demonstrated an increased RAGE expression in atherosclerotic carotid plaques compared with that in normal arteries. Furthermore, compared with the corresponding wild-type genotype, the rs2269422 single-nucleotide polymorphism of RAGE was associated with the susceptibility of patients with CAD to atherosclerosis. Furthermore, reverse transcription polymerase chain reaction and western blot analyses indicated increased coronary artery RAGE mRNA levels and protein expression, respectively, in CAD patients vs. control subjects. Furthermore, the plasma levels of S100B in CAD patients that were carriers of the AA/AT genotype of the rs2269422 variant of RAGE was increased compared with that in TT genotype carriers; as this was also identified in control subjects, it may not be CAD-specific. The RAGE rs2269422 variant is therefore significantly associated with an increased occurrence of CAD in the present Han Chinese population. Thus, RAGE variants significantly impact the risk of CAD in Han Chinese subjects.