title: Pro-inflammatory cytokine single nucleotide polymorphisms in Kawasaki disease.
abstract: OBJECTIVE
  Kawasaki disease (KD) is a systemic vasculitis of children associated with cardiovascular sequelae. Proinflammatory cytokines play a major role in KD pathogenesis. However, their role is both influenced and modified by regulatory T-cells. IL-1 gene cluster, IL-6 and TNF-α polymorphisms have shown significant associations with some vasculitides. Herein we investigated their role in KD.
  
  
  METHODS
  Fifty-five patients with KD who were randomly selected from referrals to the main pediatric hospital were enrolled in this case-control study. Single nucleotide polymorphisms (SNPs) of the following genes were assessed in patients and 140 healthy subjects as control group: IL-1α at -889 (rs1800587), IL-1β at -511 (rs16944), IL-1β at +3962 (rs1143634), IL-1R at Pst-I 1970 (rs2234650), IL-1RN/A at Mspa-I 11100 (rs315952), TNF-α at -308 (rs1800629), TNF-α at -238, IL-6 at -174 (rs1800795) and IL-6 at +565.
  
  
  RESULTS
  Twenty-one percent of the control group had A allele at TNF-α -238 while only 8% of KD patients had A allele at this position (P = 0.003, OR [95%CI] = 0.32 [0.14-0.71]). Consistently, TNF-α genotype GG at -238 had significant association with KD (OR [95% CI] = 4.31 [1.79-10.73]). Most controls carried the CG genotype at IL-6 -174 (n = 93 [66.9%]) while GG genotype was the most common genotype (n = 27 [49%]) among patients. Carriers of the GG haplotype at TNF-α (-308, -238) were significantly more prevalent among the KD group. No association was found between IL-1 gene cluster, allelic or haplotypic variants and KD.
  
  
  CONCLUSIONS
  TNF-α GG genotype at -238 and GG haplotype at positions -308 and -238 were associated with KD in an Iranian population.
authors.affiliation: Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Department of Pediatrics, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Raheleh
authors.initials: R
authors.lastname: Assari
authors.affiliation: Department of Pediatrics, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Aghighi
authors.affiliation: Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Department of Pediatrics, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Vahid
authors.identifier: http://orcid.org/0000-0003-4648-3573
authors.initials: V
authors.lastname: Ziaee
authors.affiliation: Department of Immunology, Molecular Immunology Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Sadr
authors.affiliation: Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Rahmani
authors.affiliation: Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Arezou
authors.initials: A
authors.lastname: Rezaei
authors.affiliation: Department of Immunology, Molecular Immunology Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Sadr
authors.affiliation: Department of Pediatrics, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Moradinejad
authors.affiliation: Department of Pediatrics, Vali-e-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Reza
authors.initials: SR
authors.lastname: Raeeskarami
authors.affiliation: Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.|Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.|Network of Immunity in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
authors.forename: Nima
authors.initials: N
authors.lastname: Rezaei
mesh_terms: D016009:Chi-Square Distribution; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007223:Infant; D053582:Interleukin-1alpha / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007492:Iran; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017472:Receptors, Interleukin-1 / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: C508584:IL1A protein, human; C508585:IL1B protein, human; C508600:IL6 protein, human; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha
keywords: Kawasaki disease; cytokine; interleukin-1; interleukin-6; single nucleotide polymorphisms