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

Abstract

Background: Increasing evidence shows that inflammation plays an important role in the occurrence and progression of acute ischemic stroke. The receptor for advanced glycation end products (RAGE) has been documented to involve in the pathogenic mechanisms of a variety of neurological diseases, including ischemic stroke (IS). However, the impact of RAGE gene polymorphisms on the susceptibility to IS has not been reported. We thus explored the association between RAGE gene polymorphisms and the susceptibility to IS. Method: A total of 384 patients with IS and 425 healthy controls were enrolled in this study. Three genetic polymorphisms of RAGE gene (82G/S, -429T/C and -374T/A) were determined. The serum levels of soluble RAGE (sRAGE), intetleukin-6 (IL-6), high sensitivity-C reaction protein (hs-CRP) and plasminogen activator inhibitor-1 (PAI-1) were detected. Results: Among the studied polymorphisms, only the polymorphism at 82G/S of RAGE gene was associated with the risk for ischemic stroke irrespective of the stroke subtypes. The 82S/S homozygote carriers had a significantly increased risk for ischemic stroke [adjusted odds ratio (OR): 2.297; p<0.001]. The haplotype analyses showed that the C_-429S₈₂T_-374 and T_-429S₈₂A_-374 had higher risk to develop IS (OR=1.864 and 1.931, respectively, all p<0.01), while the C_-429G₈₂T_-374 showed a protective effect against IS susceptibility (OR=0.568, p=0.001). In addition, the 82S/S homozygote carriers had a higher inflammatory level compared with 82G/S and 82G/G genotypes, indicated by lower serum sRAGE level, higher serum IL-6, hs-CRP and PAI-1 levels. The polymorphisms at -374 and -429 loci did not influence the stroke risk and the above mentioned inflammation cytokines. Conclusion: Our results showed a close correlation between the 82G/S polymorphism and the susceptibility to IS, suggesting the 82G/S polymorphism may be used as a genetic marker for the prediction of stroke occurrence in high risk subjects.

Age and genetic determinants of variation of circulating levels of the receptor for advanced glycation end products (RAGE) in the general human population

“…The assumption that the genetic factors contribute to the variation in sRAGE was made in several earlier reports (Gaens et al, 2009;Cui et al, 2013) but this has not been tested using familial data. The studies found that the polymorphisms mapped to the gene encoding RAGE (6p21.3) are significantly associated with sRAGE.…”

“…However, the specific genetic factors responsible for these correlations remain to be established. Genetic variants in the RAGE gene, associated with sRAGE level variation (Cui et al, 2013;Ng et al, 2013), could be the candidate for polymorphisms. On the other hand, genetic polymorphisms in FTO (Prakash et al, 2011;Livshits et al, 2012) and other genes associated with obesity may also contribute to the above correlation.…”

Association of RAGE gene Gly82Ser polymorphism with coronary artery disease and ischemic stroke

“…[19,20] Meanwhile, the role of Gly82Ser polymorphism in IS susceptibility remains controversial. [21,22] …”

Polymorphism -433 C>T of the Osteopontin Gene is Associated with the Susceptibility to Develop Gliomas and their Prognosis in a Chinese Cohort

“…The authors found that the -443CC genotype had higher levels of OPN mRNA compared with other allelic variants and -443C>T variants might influence the OPN mRNA levels via binding of c-Myb transcription factor [33]. In oral squamous cell carcinoma (OSCC) patients, more prevalent -443 T/T genotype was found in OSCC patients [34,35]. Our data showed that -443C>T was significantly related to the gliomas risk.…”