Molekularni markeri poremećaja koagulacije, inflamacije, apoptoze, formiranja i remodelovanja koštanog tkiva kod Leg-Kalve-Pertesove bolesti

Abstract

Leg-Kalve-Pertesova (LKP) bolest je idiopatska avaskularna osteonekroza epifize femura. Etiologija ove bolesti je nepoznata. Uprkos 100 godina istraživanja mehanizma njene patofiziologije i detaljnog opisivanja kliniĉkih i radioloških karakteristika, LKP bolest i dalje predstavlja jednu od najkontroverznijih bolesti u oblasti pedijatrijske ortopedije. Smatra se da je ova bolest multifaktorijalna, izazvana kombinacijom sredinskih i genetiĉkih faktora, ali se o genetiĉkim faktorima koji doprinose njenom razvoju vrlo malo zna. Glavni cilj ovog istraživanja je bio da se analiziraju molekularni markeri procesa koagulacije, inflamacije, apoptoze, formiranja i remodelovanja koštanog tkiva u LKP bolesti. Rezultati ovog istraživanja mogu doprineti identifikovanju prediktivnih genetiĉkih i molekularnih markera, što bi pomoglo u postavljanju dijagnoze i razvoju novih terapijskih pristupa, koji bi omogućili skraćenje perioda tokom kojeg je glava femura podložna deformitetu. Koagulacioni faktori su bili prvi genetiĉki faktori za koje se pretpostavilo da bi mogli doprineti razvoju LKP bolesti, meĊutim dobijeni su kontroverzni rezultati. Zbog toga je jedan od ciljeva ovog istraživanja bio analiza asocijacije varijanti gena ĉiji produkti uĉestvuju u procesu koagulacije: Faktor V G1691A (Leiden mutacija) (rs6025), Faktor II G20210A (rs1799963), MTHFR C677T (rs1801133) i PAI-1 4G/5G (rs1799889) sa pojavom LKP bolesti kod pacijenata iz Srbije. Navedene genske varijante su analizirane PCR-RFLP metodom i direktnim sekvenciranjem PCR fragmenta. PoreĊenjem uĉestalosti genotipova i alela navedenih genskih varijanti izmeĊu grupe pacijenata i kontrolne grupe nije pronaĊena statistiĉki znaĉajna razlika...

Legg-Calve-Perthes (LCP) disease is the idiopathic avascular osteonecrosis of the hip in children, with an unknown etiology. Despite nearly 100 years of detailed characterization of its clinical and radiological features, as well as a research devoted to the pathophysiology of this disease, LCP disease still remains one of the most controversial conditions in pediatric orthopedics. The prevailing view is that LCP disease is a multifactorial, caused by a combination of environmental and genetic factors, but the contribution of genetic factors remains largely unknown. The main objective of this study was to analyse the molecular markers of coagulation, inflammation, and apoptosis processes, as well as formation and bone remodeling in LCP disease. The obtained knowledge could contribute to the identification of the predictive genetic and molecular markers that would help in the diagnosis and development of new therapeutic approaches that would shorten the period during which the femoral head is susceptible to deformation. Coagulation factors were the first genetic factors suspected to have a role in the pathogenesis of this disease, but studies have shown inconsistent results. For this reason, one of the aims of this study was to analyse the association of variants of genes involved in coagulation: FV G1691A (Leiden mutation) (rs6025), FII G20210A (rs1799963), MTHFR C677T (rs1801133) and PAI-1 4G/5G (rs1799889), with LCP disease, in a patient group from Serbia. These genetic variants were determined by PCR-RFLP and direct sequencing methods. When genotype and allele frequencies of these genetic variants were compared among patient and control groups, no significant differences were observed...