Abstract
Introduction: Osteonecrosis (ON) is a multifactorial disease that leads to hip destruction. Lately, much focus has been at femoral head preservation with nonsurgical methods. In this study we examined the polymorphisms of IL-1α, IL-1R, IL-1RA, IL-4Rα, IL-1β, IL-12,γIFN, TGF-β, TNF-a, IL-2, IL-4, IL-6 and IL-10 genes for evaluation of their contribution in ON.Material and methods: DNA was extracted from 112 ON patients and 438 healthy donors. Analysis of the polymorphisms was completed using the PCR-SSP method. Statistical analysis was performed using theχ2test to compare the genotype and allelic frequency distribution.Results: The CT and GA genotypes of the IL-1α(-889) and TNF-a (-238) genes were found higher in the patients (51.8% and 10.8%, respectively) compared to the healthy donors (39.7% and 2.1%, respectively). In TGF-βcodon 25, the G to C polymorphism in the homozygous state was found in 1.8% of the patients and the C allele frequency was 8.9%, whereas the G allele frequency was 91.1%. Also, at the IL-10 (-1082) gene the GG genotype was 16.2% in the controls whereas in the patients was 7.2%.Conclusions: Based on the above, we showed that certain genotypes of the IL-1α, TGF-β, IL-10 and TNF-a genes could be related in the pathogenesis of a complicated disease, such as osteonecrosis. The presence of one of the above mentioned polymorphisms or the simultaneous carriage of more than one may further increase the risk for osteonecrosis, especially in those at high risk, such as patients receiving corticosteroids.
Highlights
Osteonecrosis (ON) is a multifactorial disease that leads to hip destruction
In this study we tried to evaluate the contribution of specific gene polymorphisms of several cytokines in osteonecrosis, a disease where osteoclasts-osteoblasts balance is crucial for bone remodeling
Osteonecrosis is a disease of unknown pathogenesis that usually progresses to hip joint destruction necessitating total hip arthroplasty
Summary
Osteonecrosis (ON) is a devastating disease usually leading to hip joint destruction in the third through fifth decades of life (average age, 36 years) [12,34, 35,40]. The net result is weakening of subchondral bone with subsequent collapse of the articular surface [27] This can lead to eventual collapse of the architectural bony structure of the femoral head, leading to joint pain and loss of function [3]. Several molecular pathways regulate the balance between osteoclasts and osteoblasts and determine the rate of bone remodeling. Certain cytokines such as IL1, TNF-a and other proinflammatory cytokines stimulate osteoclasts differentiation and activation [36]. In this study we tried to evaluate the contribution of specific gene polymorphisms of several cytokines in osteonecrosis, a disease where osteoclasts-osteoblasts balance is crucial for bone remodeling. We examined samples from patients with osteonecrosis and normal samples for the polymorphisms within the genes of IL-1α, IL-1R, IL-1RA, IL-4Rα, IL-1β, IL-12, γIFN, TGF-β, TNF-a, IL-2, IL-4, IL-6 and IL-10
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