doiSerbia

Association of gene variants in TLR4 and IL-6 genes with Perthes disease

Srzentić Sanja (Institute of Molecular Genetics and Genetic Engineering, Belgrade)
Spasovski Vesna (Institute of Molecular Genetics and Genetic Engineering, Belgrade)
Spasovski Duško (Faculty of Medicine, Belgrade + Institute for Orthopedic Surgery “Banjica”, Belgrade)
Živković Zorica (Clinical Hospital Center “Dr Dragiša Mišović”, Belgrade)
Matanović Dragana (Faculty of Medicine, Belgrade + Clinical Center of Serbia, Clinic for Physical Medicine and Rehabilitation, Belgrade)
Baščarević Zoran (Faculty of Medicine, Belgrade + Institute for Orthopedic Surgery “Banjica”, Belgrade)
Terzić-Šupić Zorica (Faculty of Medicine, Belgrade)
Stojiljković Maja (Institute of Molecular Genetics and Genetic Engineering, Belgrade)
Karan-Đurašević Teodora (Institute of Molecular Genetics and Genetic Engineering, Belgrade)
Stanković Biljana (Institute of Molecular Genetics and Genetic Engineering, Belgrade)
Pavlović Sonja (Institute of Molecular Genetics and Genetic Engineering, Belgrade)
Nikčević Gordana (Institute of Molecular Genetics and Genetic Engineering, Belgrade)
Vukašinović Zoran (Faculty of Medicine, Belgrade + Institute for Orthopedic Surgery “Banjica”, Belgrade)

Introduction. 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, Thr399Ile) and IL-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.

Keywords: gene variants, inflammation, Perthes disease

Projekat Ministarstva nauke Republike Srbije, br. III41004