Επίδραση των γονιδιακών πολυμορφισμών C242T, A640G και A930G στο γονίδιο της P22PHOX υπομονάδας της NADPH - οξειδάσης και του γονιδιακού πολυμορφισμού -1607 1G/2G στον υποκινητή του γονιδίου της MATRIX metalloproteinase 1 (MMP-1) στον κίνδυνο εκδήλωσης οστεοαρθρίτιδας γόνατος στο ελληνικό πληθυσμό

Abstract

Introduction. Osteoarthritis (OA) is the most common form of arthritis with still unknownpathogenic etiology and considerable contribution of genetic factors. Recently,a new emerging role of oxidative stress in the pathology of OA has beenreported, lacking however elucidation of the underlying mechanism.Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase being acomplex enzyme produced by chondrocytes, presents the major source ofreactive oxygen species (ROS) and main contributor of increased oxidativestress. One of the reasons of cartilage degradation in OA is enzymaticproteolysis of the extracellular matrix by metalloproteinases (MMPs). MMP-1,produced by chondrocytes and synovial cells, is a major proteinase of theMMPs family. The present study aims to evaluate the association of NADPHoxidase p22phox gene C242T, A640G and -A930G polymorphisms andMMP1 gene -1607 1G/2G polymorphism with primary knee OA in the Greekpopulation.Materials and MethodsOne hundred fifty five patients with primary symptomatic knee OA participatedin the study along with 139 matched controls. Genotypes were determinedusing polymerase chain reaction and restriction fragment lengthpolymorphism (PCR - RLFP) technique. Allelic and genotypic frequencieswere compared between both study groups.ResultsNo significant difference was detected for NADPH p22phox C242T andA640G polymorphisms (P>0.05). –A930G polymorphism was significantly associated with knee OA in the crude analysis (P= 0.018). The associationbetween –A930G polymorphism and knee OA disappeared when the resultswere adjusted for obesity (P= 0.078, OR: 0.54, 95%CI: 0.272-1.071). Therewas no significant association between MMP1 -1607 1G/2G polymorphismand knee OA, in crude analysis; however after multiple logistic regressionanalysis, 1G/2G was associated with reduced odds of knee OA by 75% inmales, compared to genotypes 1G/1G+2G/2G, adjusting for age and BMI(adjusted OR: 0.25, 95% CI: 0.069, 0.910, p-value=0.035). The interactionbetween all four polymorphisms was not significant.ConclusionsThe present study shows that NADPH oxidase p22phox gene C242T andA640G are not risk factors for knee OA susceptibility in the Greek population.–A930G and MMP1 -1607 1G/2G polymorphisms might contribute to knee OApathogenesis. Further studies are needed to give a global view of theimportance of this polymorphisms in the pathogenesis of OA.