Proximal interleukin-10 gene polymorphisms in Italian patients with systemic sclerosis

L. Beretta, F. Cappiello, M. Barili, R. Scorza

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Interleukin-10 (IL-10) can favour the development of fibrosis by promoting a relative shift towards T helper 2 responses. Three single base pair substitutions in the 5′ flanking region of the IL-10 gene (G/A -1082, C/T -819 and C/A -592) influence the amount of IL-10 secreted in cell cultures: the GCC haplotype is associated with an increased production, while the ACC and the ATA haplotypes are associated with intermediate and decreased production. Accordingly, three phenotypes have been individuated: high producers (GCC +/GCC +), medium producers (GCC +/GCC -) and low producers (GCC -/GCC -). We hypothesised that IL-10 haplotypes and genotypes are differently expressed in patients with systemic sclerosis (SSc) with the limited cutaneous SSc (lcSSc) subset or the diffuse cutaneous SSc (dcSSc) subset. One hundred and sixty-one unrelated Italian patients with SSc and 94 controls have been included. Their DNA was extracted and stored before being analysed by polymerase chain reaction with sequence-specific primers. The GCC haplotype is overrepresented in patients with SSc; subjects with dcSSc were the primary contributors to these results (dcSSc: 52.2% vs controls: 37.2%; χ 2 = 8.519, 2 d.f., corrected P = 0.04). In Scl70-positive patients, the GCC haplotype increased the likelihood of presenting the dcSSc subset [χ 2 = 12.56, P <0.0005; odds ratio (OR) = 3.89, 95% confidence interval (CI 95) = 1.69-9.08]; these results were confirmed at the phenotypic level (χ 2 = 11.67, 2 d.f., P = 0.003). In Scl70-positve patients, the high-producing phenotype was associated with poor survival, independently from disease subset and gender (hazard ratio = 9.9, CI 95 = 1.6-61.27, P <0.05). The IL-10 haplotype and genotype associated with high IL-10 production may alter the susceptibility to SSc and/or its expression, increasing the prognostic value of other well-known markers of disease severity.

Original languageEnglish
Pages (from-to)305-312
Number of pages8
JournalTissue Antigens
Volume69
Issue number4
DOIs
Publication statusPublished - Apr 2007

Fingerprint

Systemic Scleroderma
Polymorphism
Interleukin-10
Haplotypes
Genes
Skin
Genotype
Phenotype
Diffuse Scleroderma
5' Flanking Region
Polymerase chain reaction
Cell culture
Base Pairing
Hazards
Fibrosis
Substitution reactions
Cell Culture Techniques
Odds Ratio
Confidence Intervals
Polymerase Chain Reaction

Keywords

  • Interleukin-10
  • Polymorphism
  • Systemic sclerosis

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Proximal interleukin-10 gene polymorphisms in Italian patients with systemic sclerosis. / Beretta, L.; Cappiello, F.; Barili, M.; Scorza, R.

In: Tissue Antigens, Vol. 69, No. 4, 04.2007, p. 305-312.

Research output: Contribution to journalArticle

Beretta, L. ; Cappiello, F. ; Barili, M. ; Scorza, R. / Proximal interleukin-10 gene polymorphisms in Italian patients with systemic sclerosis. In: Tissue Antigens. 2007 ; Vol. 69, No. 4. pp. 305-312.
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abstract = "Interleukin-10 (IL-10) can favour the development of fibrosis by promoting a relative shift towards T helper 2 responses. Three single base pair substitutions in the 5′ flanking region of the IL-10 gene (G/A -1082, C/T -819 and C/A -592) influence the amount of IL-10 secreted in cell cultures: the GCC haplotype is associated with an increased production, while the ACC and the ATA haplotypes are associated with intermediate and decreased production. Accordingly, three phenotypes have been individuated: high producers (GCC +/GCC +), medium producers (GCC +/GCC -) and low producers (GCC -/GCC -). We hypothesised that IL-10 haplotypes and genotypes are differently expressed in patients with systemic sclerosis (SSc) with the limited cutaneous SSc (lcSSc) subset or the diffuse cutaneous SSc (dcSSc) subset. One hundred and sixty-one unrelated Italian patients with SSc and 94 controls have been included. Their DNA was extracted and stored before being analysed by polymerase chain reaction with sequence-specific primers. The GCC haplotype is overrepresented in patients with SSc; subjects with dcSSc were the primary contributors to these results (dcSSc: 52.2{\%} vs controls: 37.2{\%}; χ 2 = 8.519, 2 d.f., corrected P = 0.04). In Scl70-positive patients, the GCC haplotype increased the likelihood of presenting the dcSSc subset [χ 2 = 12.56, P <0.0005; odds ratio (OR) = 3.89, 95{\%} confidence interval (CI 95) = 1.69-9.08]; these results were confirmed at the phenotypic level (χ 2 = 11.67, 2 d.f., P = 0.003). In Scl70-positve patients, the high-producing phenotype was associated with poor survival, independently from disease subset and gender (hazard ratio = 9.9, CI 95 = 1.6-61.27, P <0.05). The IL-10 haplotype and genotype associated with high IL-10 production may alter the susceptibility to SSc and/or its expression, increasing the prognostic value of other well-known markers of disease severity.",
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AB - Interleukin-10 (IL-10) can favour the development of fibrosis by promoting a relative shift towards T helper 2 responses. Three single base pair substitutions in the 5′ flanking region of the IL-10 gene (G/A -1082, C/T -819 and C/A -592) influence the amount of IL-10 secreted in cell cultures: the GCC haplotype is associated with an increased production, while the ACC and the ATA haplotypes are associated with intermediate and decreased production. Accordingly, three phenotypes have been individuated: high producers (GCC +/GCC +), medium producers (GCC +/GCC -) and low producers (GCC -/GCC -). We hypothesised that IL-10 haplotypes and genotypes are differently expressed in patients with systemic sclerosis (SSc) with the limited cutaneous SSc (lcSSc) subset or the diffuse cutaneous SSc (dcSSc) subset. One hundred and sixty-one unrelated Italian patients with SSc and 94 controls have been included. Their DNA was extracted and stored before being analysed by polymerase chain reaction with sequence-specific primers. The GCC haplotype is overrepresented in patients with SSc; subjects with dcSSc were the primary contributors to these results (dcSSc: 52.2% vs controls: 37.2%; χ 2 = 8.519, 2 d.f., corrected P = 0.04). In Scl70-positive patients, the GCC haplotype increased the likelihood of presenting the dcSSc subset [χ 2 = 12.56, P <0.0005; odds ratio (OR) = 3.89, 95% confidence interval (CI 95) = 1.69-9.08]; these results were confirmed at the phenotypic level (χ 2 = 11.67, 2 d.f., P = 0.003). In Scl70-positve patients, the high-producing phenotype was associated with poor survival, independently from disease subset and gender (hazard ratio = 9.9, CI 95 = 1.6-61.27, P <0.05). The IL-10 haplotype and genotype associated with high IL-10 production may alter the susceptibility to SSc and/or its expression, increasing the prognostic value of other well-known markers of disease severity.

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