BACKGROUND: The receptor for advanced glycation end products (RAGE) and its proinflammatory ligand, S100-calgranulins, are critically implicated in the pathological progression of multiple sclerosis (MS). A functional polymorphism within the V-type immunoglobulin domain of RAGE gene, p.82G>S (c.557G>A), has been shown to affect ligand binding affinity and thus may affect susceptibility to MS. METHODS: The RAGE p.82G>S polymorphism was genotyped in 144 MS patients and 156 healthy controls using polymerase chain reaction - restriction fragment length polymorphism. A replication study was performed on a second cohort comprising 138 patients and 150 controls. The relationship between the RAGE p.82G>S polymorphism and circulating levels of soluble RAGE (sRAGE), a secreted decoy receptor against RAGE signaling, was also investigated. RESULTS: In both initial and replication cohorts, an increased MS risk was detected in RAGE p.82G>S variant allele carriers (odds ratio [OR] = 1.786, p = 0.0134 and OR = 1.732, p = 0.0210, respectively). This association signal persisted in subgroups of women and patients with relapsing-remitting MS. Moreover, compared with the wild-type 82GG carriers, carriers of the variant allele presented a faster progression of disability and a reduced serum sRAGE level. CONCLUSIONS: The present study provides preliminary evidence that the gain-of-function p.82G>S polymorphism in the RAGE gene is associated with an increased risk of MS in the Chinese population.
BACKGROUND: The receptor for advanced glycation end products (RAGE) and its proinflammatory ligand, S100-calgranulins, are critically implicated in the pathological progression of multiple sclerosis (MS). A functional polymorphism within the V-type immunoglobulin domain of RAGE gene, p.82G>S (c.557G>A), has been shown to affect ligand binding affinity and thus may affect susceptibility to MS. METHODS: The RAGE p.82G>S polymorphism was genotyped in 144 MS patients and 156 healthy controls using polymerase chain reaction - restriction fragment length polymorphism. A replication study was performed on a second cohort comprising 138 patients and 150 controls. The relationship between the RAGE p.82G>S polymorphism and circulating levels of soluble RAGE (sRAGE), a secreted decoy receptor against RAGE signaling, was also investigated. RESULTS: In both initial and replication cohorts, an increased MS risk was detected in RAGE p.82G>S variant allele carriers (odds ratio [OR] = 1.786, p = 0.0134 and OR = 1.732, p = 0.0210, respectively). This association signal persisted in subgroups of women and patients with relapsing-remitting MS. Moreover, compared with the wild-type 82GG carriers, carriers of the variant allele presented a faster progression of disability and a reduced serum sRAGE level. CONCLUSIONS: The present study provides preliminary evidence that the gain-of-function p.82G>S polymorphism in the RAGE gene is associated with an increased risk of MS in the Chinese population.
Authors: Maria B Sukkar; Md Ashik Ullah; Wan Jun Gan; Peter A B Wark; Kian Fan Chung; J Margaret Hughes; Carol L Armour; Simon Phipps Journal: Br J Pharmacol Date: 2012-11 Impact factor: 8.739
Authors: Ye Yao; Junli Zhuang; You Li; Bao Jing; Hali Li; Jingbo Li; Changgang Shao; Keshen Li; Haiyang Wang Journal: Biomed Res Int Date: 2015-02-18 Impact factor: 3.411