title: Functional polymorphism in exon 5 and variant haplotype of the interleukin-1 receptor-associated kinase 1 gene are associated with susceptibility to and severity of sepsis in the Chinese population.
abstract: BACKGROUND
  The interleukin-1 (IL-1) receptor-associated kinase 1 (IRAK1) is believed to play an important role in the pathogenesis of sepsis. Recent studies have suggested that the IRAK1 functional genetic variant could affect the severity of sepsis in Caucasians. In this report, we have investigated whether polymorphisms at the IRAK1 gene are associated with the susceptibility to and severity of sepsis among the Chinese population.
  
  
  METHODS
  Haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected from the HapMap database. They were genotyped in 255 patients with sepsis and 260 control subjects by PCR/restriction fragment length polymorphism (RFLP) analysis. The association between the selected htSNPs and the susceptibility to and severity of sepsis were estimated by Logistic regression with adjustments for age, sex, smoking, drinking, chronic disease status, Acute Physiology and Chronic Health Evaluation (APACHE) II score and primary diseases.
  
  
  RESULTS
  rs1059702 was selected to represent the six linked htSNPs for IRAK1. Genotype frequencies of the htSNPs were in Hardy-Weinberg equilibrium for females, as were allele frequencies for both sex groups. Associations were observed in females between the htSNPs C/C genotype and increased susceptibility to sepsis (odds ratio (OR), 5.46; 95% confidence interval (CI), 1.12 - 26.67; P = 0.018), and such associations were also observed between the IRAK1 variant haplotype (CC/C-allele) and increased susceptibility to sepsis (OR, 1.68; 95% CI, 1.05 - 2.70; P = 0.031) when compared with the T/T + T/C genotype and the wild-type haplotype (TC + TT/T-allele). In the multiple organ dysfunction syndrome (MODS) subgroup, the variant haplotype was also associated with increased severity of sepsis (OR, 2.37; 95% CI, 1.13 - 4.94; P = 0.02) when compared with the wild haplotype. This association was not significant in male patients.
  
  
  CONCLUSIONS
  The functional polymorphism in exon 5 and the variant haplotype of IRAK1 gene mediate susceptibility to and severity of sepsis. IRAK1 might be a genetic risk factor for the occurrence and development of sepsis in the Chinese population.
authors.affiliation: Key Disciplines Laboratory Clinical-Medicine Henan, Department of Emergency and Neurology, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fang
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Gang-qiao
authors.initials: GQ
authors.lastname: Zhou
authors.forename: Zhi-fu
authors.initials: ZF
authors.lastname: Wang
authors.forename: Zhao-shu
authors.initials: ZS
authors.lastname: Zeng
authors.forename: Zhi-yi
authors.initials: ZY
authors.lastname: Luo
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Bao-chi
authors.initials: BC
authors.lastname: Liu
mesh_terms: D000328:Adult; D044466:Asian People; D005091:Exons / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018805:Sepsis / Q000235:genetics*
chemical_list: D053592:Interleukin-1 Receptor-Associated Kinases