Significant association of interleukin-4 gene intron 3 VNTR polymorphism with susceptibility to knee osteoarthritis

Yığıt, Serbülent; Inanir, Ahmet; Tekcan, Akın; Tural, Ercan; Öztürk, Gökhan Tuna; Kısmalı, Görkem; Karakuş, Nevin

doi:10.1016/j.gene.2013.12.060

Cited by 23 publications

(17 citation statements)

References 33 publications

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“…Furthermore, Vargiolu et al (16) suggested a positive association in an Italian population between both rs1805013 and rs1805015 located in the IL-4R gene and overall risk for hand OA, while in the subgroups analysis only the association between rs1805013 and non-erosive hand OA was significant. In addition, the possible involvement of the IL-4/IL-4R axis in the pathogenesis of OA was suggested by an association of the IL-4 intron 3 VNTR polymorphism and the incidence of knee OA in a Turkish population (17). No statistically significant associations were noted between IL-4R SNPs (rs1805015 and rs1805016) and hand OA in a Finnish study (18).…”

Section: Discussionmentioning

confidence: 99%

Association of cytokine gene polymorphisms with osteoarthritis susceptibility

et al. 2018

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Osteoarthritis (OA) is a multifactorial disease characterized by low-grade inflammatory processes that are mediated initially by the cells and factors of the innate immune system. In addition to their key role in inflammation, cytokines contribute to the pathogenesis of OA through angiogenesis and chemotaxis. The purpose of the present case-control study was to investigate a possible association of four cytokine single nucleotide polymorphisms (SNPs), IL-4R -3223C>T (rs2057768), IL-8 -251T>A (rs4073), IL-10 -1082A>G (rs1800896) and TNF -A-308G>A (rs1800629) with OA susceptibility. Genomic DNA was isolated from blood samples collected from 305 Romanian subjects (90 patients with OA and 215 controls) and the genotyping of the SNPs was performed by TaqMan allelic discrimination polymerase chain reaction using predesigned assays. Our data indicated a significant association for IL-4R rs2057768 C>T SNP. The subjects that carried the CT genotype were at a higher risk for OA (OR 2.03, 95% CI: 1.21-3.42, P=0.007) compared with those that had the CC genotype. Furthermore, the carriers of the T allele were at a 1.9 fold higher risk for OA (OR 1.92; 95% CI, 1.17-3.17; P=0.009) in a dominant model. The association remained significant only for knee OA in the subgroups analysis. No correlations were observed between the other remaining SNPs and OA. The results suggested that the IL-4R rs2057768 SNP could contribute to OA susceptibility in the Romanian population, providing novel evidence for the involvement of IL-4/IL-4R pair in the pathogenesis of OA.

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Section: Discussionmentioning

confidence: 99%

Association of cytokine gene polymorphisms with osteoarthritis susceptibility

et al. 2018

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“…The observed polymorphism of the genes encoding both IL-4 and IL-4R α may predetermine the development of OA in the joints of the hand, knee and hip joint gives reason for claiming that the interaction between IL-4 and its dedicated receptor complex is one of the elements of the pathogenesis of the disease [182–184]. The production of IL-4 is primarily determined by T cells (Th2) infiltrating the synovium of the joint by blood vessels [185, 186].…”

Section: Anti-inflammatory Cytokinesmentioning

confidence: 99%

The Role of Inflammatory and Anti-Inflammatory Cytokines in the Pathogenesis of Osteoarthritis

Wojdasiewicz

Poniatowski

Szukiewicz

2014

Mediators of Inflammation

1,182

1,079

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Osteoarthritis (OA) is the most common chronic disease of human joints. The basis of pathologic changes involves all the tissues forming the joint; already, at an early stage, it has the nature of inflammation with varying degrees of severity. An analysis of the complex relationships indicates that the processes taking place inside the joint are not merely a set that (seemingly) only includes catabolic effects. Apart from them, anti-inflammatory anabolic processes also occur continually. These phenomena are driven by various mediators, of which the key role is attributed to the interactions within the cytokine network. The most important group controlling the disease seems to be inflammatory cytokines, including IL-1β, TNFα, IL-6, IL-15, IL-17, and IL-18. The second group with antagonistic effect is formed by cytokines known as anti-inflammatory cytokines such as IL-4, IL-10, and IL-13. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of OA with respect to inter- and intracellular signaling pathways is still under investigation. This paper summarizes the current state of knowledge. The cytokine network in OA is put in the context of cells involved in this degenerative joint disease. The possibilities for further implementation of new therapeutic strategies in OA are also pointed.

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“…However, chondrocytes from OA joints have shown a decreased susceptibility to this IL-4 protective effect, leaving the cartilage unprotected, quickening the degeneration via the action of the proinflammatory cytokines cited above [77]. In addition, a polymorphism in the gene encoding IL-4 and its main receptor (IL-4Rα) could predetermine the development of OA in hand and knee joints [78,79]. It was also further reported that, when compared with healthy patients, OA patients present an elevated level of soluble IL-4Rα (sIL-4Rα) [80].…”

Section: Il-4mentioning

confidence: 99%

Osteoarthritis as a Chronic Inflammatory Disease: A Review of the Inflammatory Markers

Lana¹,

Rodrigues²

2019

Osteoarthritis Biomarkers and Treatments

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Osteoarthritis (OA) is the most prevalent joint disease and a common cause of joint pain, functional loss, and disability. In addition to macroscopic features, such as cartilage degradation with subchondral bone remodeling, hypertrophy of the joint capsule, and osteophytes formation, several cellular and molecular alterations are present in OA, which lead to a chronic low-grade inflammation. Inflammatory mediators observed in OA joints are thought to be the downstream effectors of the pathogenesis of the disease. Although cytokines are among the most extensively studied mediators of inflammation, such as IL-1β and TNF, there has been an increase in studies showing the contribution of chemokines and adipokines in OA progression. This fact is supported by recent progress, which has considerably improved knowledge of the factors involved in the development of OA and the mechanisms responsible for its progression. Therefore, the aim of this chapter is to discuss the involvement of the inflammatory response in OA maintenance, focusing on the main inflammatory markers observed in studies with OA.

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Significant association of interleukin-4 gene intron 3 VNTR polymorphism with susceptibility to knee osteoarthritis

Cited by 23 publications

References 33 publications

Association of cytokine gene polymorphisms with osteoarthritis susceptibility

Association of cytokine gene polymorphisms with osteoarthritis susceptibility

The Role of Inflammatory and Anti-Inflammatory Cytokines in the Pathogenesis of Osteoarthritis

Osteoarthritis as a Chronic Inflammatory Disease: A Review of the Inflammatory Markers

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