title: Clinical relevance of single nucleotide polymorphisms within the entire NLRP3 gene in patients with major blunt trauma.
abstract: BACKGROUND
  The nucleotide-binding oligomerization domain-like receptor (NLR) family has been recognized as comprising intracellular pattern recognition receptors in which NLRP3 (NLR family, pyrin domain containing 3) plays an important role in the initiation of host immune inflammatory responses. The genetic variants have been recognized to be critical determinants of interindividual differences in both inflammatory responses and clinical outcomes in critical illness. However, little is known about the clinical relevance of NLRP3 gene polymorphisms in critical illness.
  
  
  METHODS
  A total of 718 patients with major blunt trauma were included in this study. Six tag SNPs (tSNPs) were selected from the entire NLRP3 gene through construction of haplotype bins, and they were genotyped using a pyrosequencing method. They were analyzed in relation to sepsis morbidity rate, multiple organ dysfunction (MOD) scores and IL-1β production. Moreover, the functionality of the rs2027432 polymorphism was assessed by the observation of its effect on transcriptional activities.
  
  
  RESULTS
  Among the six tSNPs genotyped in this study, two of them (rs2027432 and rs12048215) were significantly associated with sepsis morbidity rate and MOD scores. A significant association was also observed between these two polymorphisms and IL-1β production by peripheral leukocytes in response to ex vivo lipopolysaccharide stimulation. However, no combined effects were found between these two polymorphisms. In addition, the rs2027432 polymorphism could significantly enhance the promoter activities of the NLRP3 gene.
  
  
  CONCLUSIONS
  rs2027432 and rs12048215 polymorphisms might be used as relevant risk estimates for the development of sepsis and MOD syndrome in patients with major trauma, in which rs2027432 might be a functional SNP.
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Changjiang Road 10, Yuzhong District, Chongqing, 400042, People's Republic of China.
authors: An-Qiang
authors: AQ
authors: Zhang
authors: Ling
authors: L
authors: Zeng
authors: Wei
authors: W
authors: Gu
authors: Lian-Yang
authors: LY
authors: Zhang
authors: Jian
authors: J
authors: Zhou
authors: Dong-po
authors: DP
authors: Jiang
authors: Ding-Yuan
authors: DY
authors: Du
authors: Ping
authors: P
authors: Hu
authors: Ce
authors: C
authors: Yang
authors: Jun
authors: J
authors: Yan
authors: Hai-Yan
authors: HY
authors: Wang
authors: Jian-Xin
authors: JX
authors: Jiang
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology / Q000235:genetics; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018805:Sepsis / Q000209:etiology / Q000235:genetics; D014949:Wounds, Nonpenetrating / Q000150:complications / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human