Genetic predisposition to ischaemic stroke by RAGE and HMGB1 gene variants in Chinese Han population

Abstract

Emerging evidence suggests that the multiligand receptor for advanced glycation end products (RAGE) and its ligand high mobility group box 1 protein (HMGB1) contribute to the pathophysiology of ischaemic stroke (IS). The present study aimed to investigate the association of RAGE and HMGB1 variants with the risk of IS. A total of 1,034 patients and 1,015 age- and sex-matched healthy controls were genotyped to detect five genetic variants of the RAGE gene and four genetic variants of the HMGB1 gene using the Multiplex SNaPshot assay. We found that the rs2070600 variant of RAGE was associated with an increased risk of IS (OR = 1.19, 95% CI: 1.02-1.38, P = 0.043), whereas the rs2249825 variant of HMGB1 was associated with a decreased risk of IS (OR = 0.83, 95% CI: 0.71-0.98, P = 0.041). Further stratification by IS subtypes revealed that the presence of the TT genotype of the RAGE rs2070600 variant confers a higher risk of the large artery atherosclerosis subtype of IS (P = 0.036). Moreover, patients with the variant T allele of the RAGE rs2070600 variant presented with reduced serum soluble RAGE production. Patients carrying the variant G allele of the HMGB1 rs2249825 variant exhibited significantly lower infarct volumes than those with the major CC genotype. These clues may help in the development of optimal personalized therapeutic approaches for IS patients.

Polymorphisms of Calgranulin Genes and Ischemic Stroke in a Chinese Population

“… 40 Our previous study reported that the HMGB1 rs2249825 variant was associated with low infarct volume and was a protective factor for IS in the Han Chinese population. 41 Because of the involvement of S100 calgranulins in vascular inflammation, we hypothesized that they may have a role in stroke infarct size. Patients with the variant C alleles of the S100A8 rs3795391, rs3806232, or S100A12 rs2916191 variant have greater infarct sizes than those with the major T alleles, according to the findings.…”

Association of DIAPH1 gene polymorphisms with ischemic stroke

“…Our previous study focused on the relationship between RAGE genetic variations and hypertension [20]. Positive associations between RAGE variations and IS have been observed as well [21].…”

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

“…Upon S100B binding to RAGE, a series of cellular signaling pathways is activated to induce a massive release of inflammatory factors into the blood. The expression of RAGE by inflammatory cells attracts macrophages into the lesion region, followed by accumulation of excess cholesterol in the macrophages, contributing to the formation of foam cells in atherosclerotic lesions and then enhancing the severity of the coronary artery lesion (6,32). Thus, RAGE-positive macrophages and their ligands, including S100B, have an intermediary part in regulating cell proliferation, differentiation and apoptosis in the development of atherosclerotic plaques.…”