No evidence for a role of the proximal IL‐6 G/C ‐174 single nucleotide polymorphism in Italian patients with systemic sclerosis

Beretta, Lorenzo; Santaniello, Alessandro; Cappiello, Francesco Liberato; Barili, Morena; Scorza, Raffaella

doi:10.1111/j.1582-4934.2007.00070_1.x

Cited by 4 publications

(3 citation statements)

References 14 publications

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“…To date few and relatively underpowered studies have been conducted to analyze the influence of the IL6 gene in susceptibility to SSc, and results have been controversial 24,25 . Moreover, these studies assessed only the rs1800795 polymorphism (-174G/C) and this may provide a limited view of the role of IL6 in SSc pathophysiology, because several polymorphisms are likely to modify levels of IL-6 24,25,26 . Our investigation is the first tagging study to explore the influence of most of the IL6 gene variability in the susceptibility to SSc and/or its major clinical features in a large and well-defined white cohort.…”

Section: Discussionmentioning

confidence: 99%

Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis

Cénit

Simeón²,

Vonk³

et al. 2012

J Rheumatol

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Section: Discussionmentioning

confidence: 99%

Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis

Cénit

Simeón²,

Vonk³

et al. 2012

J Rheumatol

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“…Moreover, recent evidences have suggested that IL‐6 may be involved in the endothelial cell dysfunction leading to the vascular damage in SSc patients . The rs1800795 (−174G/C) genetic variant located in the IL6 gene promoter region has been correlated with the IL6 gene transcriptional activity , although it does not seem to confers susceptibility to SSc . However, IL‐6 function is mainly controlled by its receptor (IL‐6R), and it is likely that genetic variants affecting the conformation of this protein may potentially contribute to SSc susceptibility and/or its major clinical manifestations.…”

Section: Genotype and Minor Allele Frequencies Of Snps Located Withinmentioning

confidence: 99%

No evidence of association between functional polymorphisms located within IL6R and IL6ST genes and systemic sclerosis

et al. 2012

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Systemic sclerosis (SSc) is a complex autoimmune disease which genetic component has not been yet completely understood. IL6 encodes a cytokine with a crucial role in the development of autoimmunity and fibrosis and its actions mainly are controlled by IL-6 receptor (IL-6R). We aimed to investigate whether the functional genetic variants rs8192284 and rs2228044 previously associated with several autoimmune diseases, located within the IL-6 receptor (IL-6R) subunits IL6R and IL6ST genes, respectively, are involved in the susceptibility to SSc and/or its major clinical subphenotypes. A Spanish cohort including 1013 SSc patients and 1375 controls was genotyped using the TaqMan® allelic discrimination technology. SSc patients were subdivided according to the major clinical forms, autoantibody status and presence of fibrotic lung affection. Our data showed no influence of the selected variants in global SSc susceptibility (rs8192284: P=0.67, odds ratios (OR)=0.98; rs2228044: P=0.99, OR=1.00). Similarly, the clinical/autoantibody subphenotype analyses did not yielded significant results. Our data suggest that the analyzed polymorphisms may not play a significant role in the SSc susceptibility.

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“…Because cytokine production is regulated at the genetic level (11–14), it has been hypothesized that single‐nucleotide polymorphisms (SNPs) in or near cytokine genes may be relevant to the development of SSc. Nonetheless, studies conducted so far on this matter have often yielded disappointing results (15–17) and, in some cases, the associations described by some authors have not been confirmed in replication studies conducted in other independent populations (16, 18–20). These contradictory results could be ascribed to different factors.…”

Section: Introductionmentioning

confidence: 98%

Ability of epistatic interactions of cytokine single‐nucleotide polymorphisms to predict susceptibility to disease subsets in systemic sclerosis patients

Beretta¹,

Cappiello²,

Moore³

et al. 2008

Arthritis & Rheumatism

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Objective. Gene-gene interaction, or epistasis, is considered a ubiquitous component of complex human diseases such as systemic sclerosis (SSc). Epistasis is difficult to model by traditional parametric approaches; therefore, nonparametric computational algorithms, such as multifactor dimensionality reduction (MDR), have been developed. Methods. A total of 242 consecutive unrelated Italian SSc patients and an equal number of well-matched healthy controls were genotyped for 22 cytokine single-nucleotide polymorphisms (SNPs; 13 cytokine genes). The distribution of the SNPs between controls and SSc patients, controls and limited cutaneous SSc (lcSSc) patients, and controls and diffuse cutaneous SSc (dcSSc) patients was tested by the MDR constructive induction algorithm and by focused interaction testing framework (FITF), a logistic regression-based approach. Results. None of the studied SNPs had main independent effects on SSc or disease subset susceptibility, therefore no epistatic interaction was detectable by FITF. The MDR analysis showed a significant epistatic interaction among the interleukin-2 (IL-2) G-330T, IL-6 C-174G, and interferon-␥ AUTR5644T SNPs and the IL-1 receptor Cpst1970T, IL-6 Ant565G, and IL-10 C-819T SNPs in lcSSc and dcSSc susceptibility, respectively. The relevance of the single multilocus attributes constructed by the MDR inductive algorithm was then confirmed by the parametric approach (P < 0.001 for both controls versus lcSSc patients and controls versus dcSSc patients). Conclusion. We provide evidence for gene-gene interaction among cytokine SNPs in the context of SSc. The interaction among cytokine SNPs with a profibrotic or a regulatory function on profibrotic interleukins is relevant to the susceptibility to SSc subsets and it appears to be more important than the contribution of any single cytokine SNP.

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No evidence for a role of the proximal IL‐6 G/C ‐174 single nucleotide polymorphism in Italian patients with systemic sclerosis

Cited by 4 publications

References 14 publications

Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis

Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis

No evidence of association between functional polymorphisms located within IL6R and IL6ST genes and systemic sclerosis

Ability of epistatic interactions of cytokine single‐nucleotide polymorphisms to predict susceptibility to disease subsets in systemic sclerosis patients

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