A polymorphic variant inside the osteopontin gene shows association with disease course in oligoarticular juvenile idiopathic arthritis

Marciano, Renato; Giacopelli, Francesca; Divizia, Maria Teresa; Gattorno, Marco; Felici, Enrico; Pistorio, Angela; Martini, Alberto; Ravazzolo, Roberto; Picco, Paolo

doi:10.1136/ard.2005.040626

Cited by 14 publications

(7 citation statements)

References 20 publications

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“…Some, but not all, cytokine gene associations distinguish the subtypes (Table 4). The association of a low-expression-level allele of osteopontin with persistent oligoarticular JIA is consistent with the more-limited disease observed in this subtype as compared with extended oligoarticular JIA, and further argues for a pathogenic distinction between the two forms of oligoarticular JIA (45). Overall, observed genetic associations lend further support to the idea that the oligoartcular and polyarticular subtypes have different etiologies, but also argue that certain immunological pathways, such as MIF-driven inflammation, could contribute to pathology across subtypes.…”

Section: Pathogenesissupporting

confidence: 72%

Oligoarticular and polyarticular JIA: epidemiology and pathogenesis

et al. 2009

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Summary Juvenile idiopathic arthritis (JIA) refers to a group of chronic childhood arthropathies, currently classified into subtypes primarily on the basis of clinical features. Research has focused on the hypothesis that these subtypes arise through distinct etiologic pathways. In this Review, we discuss four subtypes of JIA: persistent oligoarticular, extended oligoarticular, rheumatoid-factor positive polyarticular and rheumatoid-factor-negative polyarticular. These subtypes differ in prevalence between ethnic groups and are associated with different HLA alleles. Non-HLA genetic risk factors have also been identified, some of which reveal further molecular differences between these subtypes, while others suggest mechanistic overlap. Investigations of immunophenotypes also provide insights into subtype differences: adaptive immunity appears to have a prominent role in both polyarticular and oligoarticular JIA, and the more-limited arthritis observed in persistent oligoarticular JIA as compared with extended oligoarticular JIA may reflect more-potent immunoregulatory T-cell activity in the former. Tumor necrosis factor seems to be a key mediator of both polyarticular and oligoarticular JIA, especially in the extended oligoarticular subtype, although elevated levels of other cytokines also are observed. Limited data on monocytes, dendritic cells, B cells, natural killer T cells, and neutrophils suggest that the contributions of these cells differ across subtypes of JIA. Within each subtype, however, common pathways appear to drive joint damage.

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Section: Pathogenesissupporting

confidence: 72%

Oligoarticular and polyarticular JIA: epidemiology and pathogenesis

et al. 2009

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“…So far, genetic variants in the OPN gene have shown to be involved in susceptibility to other immune-mediated diseases such as SLE [59] , [60] , oligoarticular juvenile idiopathic arthritis [61] and sarcoidosis [51] . Despite promising functional data, previous genotype analyses could not confirm OPN as significant disease-modifying gene in classical Th17-mediated diseases such as multiple sclerosis [62] , [63] and rheumatoid arthritis [64] .…”

Section: Discussionmentioning

confidence: 99%

The Role of Osteopontin (OPN/SPP1) Haplotypes in the Susceptibility to Crohn's Disease

et al. 2011

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BackgroundOsteopontin represents a multifunctional molecule playing a pivotal role in chronic inflammatory and autoimmune diseases. Its expression is increased in inflammatory bowel disease (IBD). The aim of our study was to analyze the association of osteopontin (OPN/SPP1) gene variants in a large cohort of IBD patients.Methodology/Principal FindingsGenomic DNA from 2819 Caucasian individuals (n = 841 patients with Crohn's disease (CD), n = 473 patients with ulcerative colitis (UC), and n = 1505 healthy unrelated controls) was analyzed for nine OPN SNPs (rs2728127, rs2853744, rs11730582, rs11739060, rs28357094, rs4754 = p.Asp80Asp, rs1126616 = p.Ala236Ala, rs1126772 and rs9138). Considering the important role of osteopontin in Th17-mediated diseases, we performed analysis for epistasis with IBD-associated IL23R variants and analyzed serum levels of the Th17 cytokine IL-22. For four OPN SNPs (rs4754, rs1126616, rs1126772 and rs9138), we observed significantly different distributions between male and female CD patients. rs4754 was protective in male CD patients (p = 0.0004, OR = 0.69). None of the other investigated OPN SNPs was associated with CD or UC susceptibility. However, several OPN haplotypes showed significant associations with CD susceptibility. The strongest association was found for a haplotype consisting of the 8 OPN SNPs rs2728127-rs2853744-rs11730582-rs11439060-rs28357094-rs112661-rs1126772-rs9138 (omnibus p-value = 2.07×10−8). Overall, the mean IL-22 secretion in the combined group of OPN minor allele carriers with CD was significantly lower than that of CD patients with OPN wildtype alleles (p = 3.66×10−5). There was evidence for weak epistasis between the OPN SNP rs28357094 with the IL23R SNP rs10489629 (p = 4.18×10−2) and between OPN SNP rs1126616 and IL23R SNP rs2201841 (p = 4.18×10−2) but none of these associations remained significant after Bonferroni correction.Conclusions/SignificanceOur study identified OPN haplotypes as modifiers of CD susceptibility, while the combined effects of certain OPN variants may modulate IL-22 secretion.

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“…So far, genetic variants in the SPP1 gene have shown to be involved in susceptibility to other immune-mediated diseases such as SLE [8,9], oligoarticular juvenile idiopathic arthritis [26] and sarcoidosis [27]. Despite promising functional data, previous genotype analyses could not confirm SPP1 as significant disease modifying gene in classical Th17-mediated diseases such as multiple sclerosis [28,29] and rheumatoid arthritis [30].…”

Section: Discussionmentioning

confidence: 98%

A Study of the Association of Polymorphism rs5860110 and its Protective Role against Ankylosing Spondylitis in a Chinese Population

Wang¹,

Zhang²

2014

Trop. J. Pharm Res

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A polymorphic variant inside the osteopontin gene shows association with disease course in oligoarticular juvenile idiopathic arthritis

Abstract: The results suggest that osteopontin gene polymorphism is associated with the disease course in oligoarticular JIA and might therefore represent a useful genetic marker to characterise patients with oligoarticular JIA who are at risk of a worse outcome.

Cited by 14 publications

References 20 publications

Oligoarticular and polyarticular JIA: epidemiology and pathogenesis

Oligoarticular and polyarticular JIA: epidemiology and pathogenesis

The Role of Osteopontin (OPN/SPP1) Haplotypes in the Susceptibility to Crohn's Disease

A Study of the Association of Polymorphism rs5860110 and its Protective Role against Ankylosing Spondylitis in a Chinese Population

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