title: Association of gene variants in TLR4 and IL-6 genes with Perthes disease.
abstract: BACKGROUND
  Perthes disease is idiopathic avascular osteonecrosis of the hip in children, with unknown etiology. Inflammation is present during development of Perthes disease and it is known that this process influences bone remodeling.
  
  
  OBJECTIVE
  Since genetic studies related to inflammation have not been performed in Perthes disease so far, the aim of this study was to analyze the association of frequencies of genetic variants of immune response genes, toll-like receptor 4 (TLR4) and interleukin-6 (IL-6), with this disease.
  
  
  METHODS
  The study cohort consisted of 37 patients with Perthes disease and 50 healthy controls. Polymorphisms of well described inflammatory mediators: TLR4 (Asp299Gly, Thr39911e) and 11-6 (G-174C, G-597A) were determined by polymerase chain reaction restriction fragment length polymorphism method. Results IL-6 G-174C and G-597A polymorphisms were in complete linkage disequilibrium. A statistically significant increase of heterozygote subjects for IL-6 G-174C/G-597A was found in controls in comparison to Perthes patient group (p = 0.047, OR = 2.49, 95% CI = 1.00-6.21). Also, the patient group for IL-6 G-174C/G-597A polymorphisms was not in Hardy-Weinberg equilibrium. No statistically significant differences were found between patient and control groups for TLR4 analyzed polymorphisms. A stratified analysis by the age at disease onset also did not reveal any significant difference for all analyzed polymorphisms. Conclusion Our study revealed that heterozygote subjects for the IL-6 G-174C/G-597A polymorphisms were significantly overrepresented in the control group than in the Perthes patient group. Consequently, we concluded that children who are heterozygous for these polymorphisms have a lower chance of developing Perthes disease than carriers of both homozygote genotypes.
authors.forename: Sanja
authors.initials: S
authors.lastname: Srzentić
authors.forename: Vesna
authors.initials: V
authors.lastname: Spasovski
authors.forename: Dusko
authors.initials: D
authors.lastname: Spasovski
authors.forename: Zorica
authors.initials: Z
authors.lastname: Zivković
authors.forename: Dragana
authors.initials: D
authors.lastname: Matanović
authors.forename: Zoran
authors.initials: Z
authors.lastname: Bascarević
authors.forename: Zorica Terzić
authors.initials: ZT
authors.lastname: Supić
authors.forename: Maja
authors.initials: M
authors.lastname: Stojiljković
authors.forename: Teodora
authors.initials: T
authors.lastname: Karan-Djurasević
authors.forename: Biljana
authors.initials: B
authors.lastname: Stanković
authors.forename: Sonja
authors.initials: S
authors.lastname: Pavlović
authors.forename: Gordana
authors.initials: G
authors.lastname: Nikcević
authors.forename: Zoran
authors.initials: Z
authors.lastname: Vukasinović
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D007873:Legg-Calve-Perthes Disease / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D015850:Interleukin-6; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4