title: Predictive genetic markers of coagulation, inflammation and apoptosis in Perthes disease—Serbian experience.
abstract: Perthes disease is one of the most common forms of pediatric femoral head osteonecrosis with an unknown etiology. Coagulation factors were the first genetic factors suspected to have a role in the pathogenesis of this disease, but studies showed inconsistent results. It is described that inflammation is present during early stages of Perthes disease, but its genetic aspect has not been studied extensively. Little is known regarding the status of apoptotic factors during the repair process that leads to the occurrence of hip deformity in patients. Therefore, the aim of this study was to analyze major mediators involved in coagulation, inflammation, and apoptotic processes as possible causative factors of Perthes disease. The study cohort consisted of 37 patients. Gene variants of TNF-α, FV, FII, and MTHFR genes were determined by PCR-RFLP, while IL-3 and PAI-1 were genotyped by direct sequencing. The expression level of Bax, Bcl-2, Bcl2L12, Fas and FasL was analyzed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) technique. Our results showed a significantly increased level of expression of pro-apoptotic factor Bax along with significantly higher Bax/Bcl-2 ratio in the patient group.
  
  
  CONCLUSIONS
  The results presented indicate that apoptosis could be one of the factors contributing to the lack of balanced bone remodeling process in Perthes patients.
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, Belgrade, 11010, Serbia, sanjasrz@gmail.com.
authors.forename: Sanja
authors.initials: S
authors.lastname: Srzentić
authors.forename: Gordana
authors.initials: G
authors.lastname: Nikčević
authors.forename: Duško
authors.initials: D
authors.lastname: Spasovski
authors.forename: Zoran
authors.initials: Z
authors.lastname: Baščarević
authors.forename: Zorica
authors.initials: Z
authors.lastname: Živković
authors.forename: Zorica
authors.initials: Z
authors.lastname: Terzic-Šupić
authors.forename: Dragana
authors.initials: D
authors.lastname: Matanović
authors.forename: Valentina
authors.initials: V
authors.lastname: Djordjević
authors.forename: Sonja
authors.initials: S
authors.lastname: Pavlović
authors.forename: Vesna
authors.initials: V
authors.lastname: Spasovski
mesh_terms: D000293:Adolescent; D017209:Apoptosis / Q000235:genetics*; D001777:Blood Coagulation / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D053222:Fas Ligand Protein / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007377:Interleukin-3 / Q000235:genetics; D007873:Legg-Calve-Perthes Disease / Q000235:genetics* / Q000378:metabolism; D008222:Lymphokines / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011516:Prothrombin / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics*; D019014:fas Receptor / Q000235:genetics
chemical_list: C430100:BCL2L12 protein, human; D053222:Fas Ligand Protein; C089422:Fv protein, human; D005819:Genetic Markers; D007377:Interleukin-3; D008222:Lymphokines; D009124:Muscle Proteins; D017395:Plasminogen Activator Inhibitor 1; D019253:Proto-Oncogene Proteins c-bcl-2; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D011516:Prothrombin; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)