title: Identification of haplotype tag single nucleotide polymorphisms within the nuclear factor-κB family genes and their clinical relevance in patients with major trauma.
abstract: BACKGROUND
  Nuclear factor-κB (NF-κB) family plays an important role in the development of sepsis in critically ill patients. Although several single nucleotide polymorphisms (SNPs) have been identified in the NF-κB family genes, only a few SNPs have been studied.
  
  
  METHODS
  A total of 753 patients with major blunt trauma were included in this study. Tag SNPs (tSNPs) were selected from the NF-κB family genes (NFKB1, NFKB2, RELA, RELB and REL) through construction of haplotype blocks. The SNPs selected from genes within the canonical NF-κB pathway (including NFKB1, RELA and REL), which played a critical role in innate immune responses were genotyped using pyrosequencing method and analyzed in relation to the risk of development of sepsis and multiple organ dysfunction (MOD) syndrome. Moreover, the rs842647 polymorphism was analyzed in relation to tumor necrosis factor α (TNF-α) production by peripheral blood leukocytes in response to bacterial lipoprotein stimulation.
  
  
  RESULTS
  Eight SNPs (rs28362491, rs3774932, rs4648068, rs7119750, rs4803789, rs12609547, rs1560725 and rs842647) were selected from the NF-κB family genes. All of them were shown to be high-frequency SNPs in this study cohort. Four SNPs (rs28362491, rs4648068, rs7119750 and rs842647) within the canonical NF-κB pathway were genotyped, and rs842647 was associated with sepsis morbidity rate and MOD scores. An association was also observed between the rs842647 A allele and lower TNF-α production.
  
  
  CONCLUSIONS
  rs842647 polymorphism might be used as relevant risk estimate for the development of sepsis and MOD syndrome in patients with major trauma.
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Gaotanyan Street, Chongqing, 400038, China. qiangwei2@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Gaotanyan Street, Chongqing, 400038, China. zhanganqiang@126.com.
authors.forename: An Qiang
authors.initials: AQ
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Gaotanyan Street, Chongqing, 400038, China. 13996251868@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Gaotanyan Street, Chongqing, 400038, China. nutdgjw@163.com.
authors.forename: Jun Wei
authors.initials: JW
authors.lastname: Gao
authors.affiliation: Chongqing Emergency Medical Center, Jiankang Road, Chongqing, 400042, China. dudingyuan@qq.com.
authors.forename: Ding Yuan
authors.initials: DY
authors.lastname: Du
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Gaotanyan Street, Chongqing, 400038, China. hpzhangly@163.com.
authors.forename: Lian Yang
authors.initials: LY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Gaotanyan Street, Chongqing, 400038, China. zengling_1025@126.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Gaotanyan Street, Chongqing, 400038, China. dujuan1982727@163.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Gaotanyan Street, Chongqing, 400038, China. youyouswallow@126.com.
authors.forename: Hai Yan
authors.initials: HY
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Gaotanyan Street, Chongqing, 400038, China. hellojjx@126.com.
authors.forename: Jian Xin
authors.initials: JX
authors.lastname: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002681:China / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000453:epidemiology / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018805:Sepsis / Q000453:epidemiology / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014949:Wounds, Nonpenetrating / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha