title: Identification of haplotype tag single nucleotide polymorphisms within the receptor for advanced glycation end products gene and their clinical relevance in patients with major trauma.
abstract: BACKGROUND
  The receptor for advanced glycation end products (RAGE) has been considered as one of the major pattern recognition receptors and plays an important role in the development of sepsis and multiple organ dysfunction in critical illnesses. Although genetic variants of the RAGE gene have been shown to be well associated with susceptibility to some inflammatory diseases, little is known about their clinical relevance in the development of sepsis in critical ill patients.
  
  
  METHODS
  Four genetic variants were selected from the entire RAGE gene and genotyped using pyrosequencing and polymerase chain reaction-length polymorphism methods. Association studies were performed in two independent Chinese Han populations.
  
  
  RESULTS
  Among the four genetic variants, only the rs1800625 polymorphism was significantly associated with sepsis morbidity rate and multiple organ dysfunction (MOD) scores in patients with major trauma both in Chongqing (n = 496) and Zhejiang (n = 232) districts, respectively. Results from ex vivo responsiveness of peripheral blood leukocytes indicated that the rs1800625 polymorphism was well associated with decreased production of TNFα. In addition, the rs1800625 polymorphism could significantly inhibit the promoter activities of the RAGE gene.
  
  
  CONCLUSIONS
  The rs1800625 polymorphism is a functional variant, which might be used as a relevant risk estimate for the development of sepsis and multiple organ dysfunction syndrome in patients with major trauma.
authors: Ling
authors: L
authors: Zeng
authors: An-qiang
authors: AQ
authors: Zhang
authors: Wei
authors: W
authors: Gu
authors: Jian
authors: J
authors: Zhou
authors: Lian-yang
authors: LY
authors: Zhang
authors: Ding-yuan
authors: DY
authors: Du
authors: Mao
authors: M
authors: Zhang
authors: Hai-yan
authors: HY
authors: Wang
authors: Jun
authors: J
authors: Yan
authors: Ce
authors: C
authors: Yang
authors: Jian-xin
authors: JX
authors: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002681:China; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000235:genetics; D009104:Multiple Trauma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics*; D018805:Sepsis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D014409:Tumor Necrosis Factor-alpha