Association of polymorphisms in the RAGE gene with serum CRP levels and coronary artery disease in the Chinese Han population

Abstract

The role of an advanced glycation end product/receptor for advanced glycation end product (AGE/RAGE) system in the pathogenesis of coronary artery disease (CAD) is not fully understood. To clarify whether polymorphisms of the RAGE gene were related to CAD, we performed a case-control study in Chinese Han patients. The allele frequencies and genotype distribution combinations of the À429T/C, 1704G/T and G82S polymorphisms of the RAGE gene were compared in 200 cases of hypertension (HT), 155 cases of CAD combined with HT (CAD&HT), 175 cases of CAD and 170 control subjects. Polymerase chain reaction-restriction fragment length polymorphism was used for detection of genotypic variants. The S allele frequency of the G82S polymorphism was higher in the CAD (odds ratio (OR), 2.303, 95% confidence interval (CI) 1.553-3.416; Po0.001, P corr o0.003) and CAD&HT (OR, 1.842; 95% CI 1.219-2.785; Po0.003, P corr o0.009) groups when compared with the control group. However, the S allele frequency was not significantly different between the CAD and the CAD&HT patient groups (P¼0.223), and no statistically significant difference of genotype or allele frequency distributions was observed in the HT group (P40.05). Meanwhile, serum CRP was significantly associated with the G82S variant. Haplotype-based logistic regression analysis revealed that haplotype G-Ser-T (OR, 1.670; 95% CI, 1.017-2.740; P¼0.043), compared with the reference haplotype T-Gly-T, was associated with an increased risk of CAD after adjusting for other risk factors. Further analysis limited to nondiabetic participants exhibited similar significant findings. The haplotype carrying the G82S variant of the RAGE gene was significantly associated with an increased risk of CAD, but not with HT patients. Moreover, a remarkable association of the G82S variant with serum CRP levels implied that the prevalence of RAGE 82S allelic variation might influence susceptibility to CAD by affecting vascular inflammation.

Polymorphism of the RAGE Affects the Serum Inflammatory Levels and Risk of Ischemic Stroke in a Chinese Population

“…Hou et al reported that hypertensive patients had higher serum hs-CRP levels than controls with normal blood levels [55]. The serum CRP was significantly associated with the G82S variant in the Chinese Han population with CAD [41]. Serum CRP concentration has been reported to be in relation to ischemic stroke subtype.…”

“…Jang et al have reported that subjects with the SS homozygous mutation of the G82S polymorphism had increased risk factors for cardiovascular disease compared with those bearing at least one G allele in non-diabetic and non-obese Koreans [39]. G82S polymorphism in the RAGE gene is associated with diabetic retinopathy in Chinese population [40], but no positive association between the polymorphisms at 82G/S and the presence and severity of CAD [41]. The association of the G82S polymorphism of RAGE with diabetic retinopathy was confirmed in the population of southern India [42].…”

“…Recent studies reported the RAGE G82S polymorphism results in the enhancement of pro-inflammatory mechanisms in immune/ inflammatory diseases and vascular injury. There was a remarkable association of the G82S variant with elevated serum CRP levels, implying that the prevalence of RAGE 82S allelic variation may influence susceptibility to vascular disorders by affecting vascular inflammation [41]. Soluble RAGE (sRAGE) is inversely associated with chronic inflammatory state, diabetes, atherosclerosis and metabolic syndrome and may neutralize the AGEs-mediated damage by acting as a decoy [54].…”

Polymorphisms of Receptor for Advanced Glycation end Products and Risk of Epithelial Ovarian Cancer in Chinese Patients

“…The 82G>S variant also was significantly influence the serum inflammatory marker, such as C reaction protein level in the Chinese Han population with coronary heart disease [30]. Factors contributing to chronic inflammation appear to be associated with increased risk of ovarian cancer [31].…”

AGER genetic polymorphisms increase risks of breast and lung cancers

“…AGER, a cell surface protein, is a multi-ligand receptor of the immunoglobulin superfamily that is expressed in combination with certain active ligands including advanced glycosylation end-products (AGEs), amyloid-b protein, and several members of the S100 family (Gao et al, 2010). The formation of the AGER complex primarily includes components such as non-enzymatic glycation proteins and lipoproteins, and its protein structure is comprised of an extracellular domain and a single-transmembrane domain with a short cytosolic tail (Fang et al, 2010).…”