title: A functional p.82G>S polymorphism in the RAGE gene is associated with multiple sclerosis in the Chinese population.
abstract: 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.affiliation: Department of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.
authors.forename: Keshen
authors.initials: K
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Dawei
authors.initials: D
authors.lastname: Dai
authors.forename: Songpo
authors.initials: S
authors.lastname: Yao
authors.forename: Wandong
authors.initials: W
authors.lastname: Liang
authors.forename: Lifen
authors.initials: L
authors.lastname: Yao
authors.forename: Ze
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000067759:Receptor for Advanced Glycation End Products