Skip to main content
Top
Published in: Rheumatology International 11/2008

01-09-2008 | Original Article

Association between ‘interleukin’ 10 gene (IL10) polymorphisms and systemic sclerosis with interstitial lung involvement

Authors: Ö. Ates, B. Müsellim, G. Öngen, A. Topal-Sarıkaya

Published in: Rheumatology International | Issue 11/2008

Login to get access

Abstract

Systemic sclerosis (SSc), also termed as “scleroderma”, is a progressive, systemic disease of unknown origin characterized by excessive fibrosis, vascular abnormalities and immune dysfunction. Extracellular matrix (ECM) production by fibroblasts in SSc is modulated and regulated by cytokines. Since IL10 has antiinflamatory properties and, contributes to the fibrotic processes in SSc, we analyzed IL-10 gene polymorphisms including −1082 G/A, −819 C/T and −592C/A in 45 systemic sclerosis patients with lung involvement and 150 healthy control using ARMS-PCR. While no association was found between SSc and −819C/T, −592C/A polymorphism, −1082 G/A allele frequency in SSc patients was higher than that in control and significant association was found between SSc and −1082 G/A (Pc: <0.000, OR: 2.85 95% CI: 1.74–4.63). In addition significant difference was found between the frequencies of the IL-10 GCC, ACC haplotypes (Pc: <0.000, OR: 2.85, 95% CI: 1.74–4.63; Pc: 0.012, O.R: 1.56, 95% CI: 1.09–2.23, respectively), GCC+/GCC+, GCC/GCC genotypes (Pc: 0.002, OR: 5.07, 95% CI: 1.82–14.21; Pc: <0.000, O.R: 4.00, 95% CI: 1.87–8.98, respectively) and SSc. Our findings suggest that IL-10 1082 G/A alleles or haplotypes containing these alleles may play role in SSc susceptibility.
Literature
1.
go back to reference LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieq T, Medsger TA, Rowell N, Wollheim F (1998) Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 15:202–205 LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieq T, Medsger TA, Rowell N, Wollheim F (1998) Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 15:202–205
2.
go back to reference Haustein UF (2002) Systemic sclerosis-scleroderma. Dermatol Online J 8(1):3PubMed Haustein UF (2002) Systemic sclerosis-scleroderma. Dermatol Online J 8(1):3PubMed
3.
4.
go back to reference Wells AU, Hansell DM, Corrin B, Harrison NK, Goldstraw P, Black CM, du Bois RM (1992) High resolution computed tomography as a predictor of lung histology in systemic sclerosis. Thorax 47:738–742PubMedCrossRef Wells AU, Hansell DM, Corrin B, Harrison NK, Goldstraw P, Black CM, du Bois RM (1992) High resolution computed tomography as a predictor of lung histology in systemic sclerosis. Thorax 47:738–742PubMedCrossRef
5.
go back to reference Ghosh AK (2002) Factors involved in the regulation of type 1 collagen gene expression: implication in fibrosis. Exp Biol Med 227:301–314 Ghosh AK (2002) Factors involved in the regulation of type 1 collagen gene expression: implication in fibrosis. Exp Biol Med 227:301–314
6.
go back to reference Akdis CA, Blaser K (2001) Mechanisms of interleukin-10 mediated immune suppression. Immunology 103:131–136PubMedCrossRef Akdis CA, Blaser K (2001) Mechanisms of interleukin-10 mediated immune suppression. Immunology 103:131–136PubMedCrossRef
7.
go back to reference Reitamo S, Remitz A, Tamai K, Uitto J (1994) Interleukin 10 modulates type 1 collagen and matrix metalloprotease gene expression in cultured human skin fibroblasts. J Clin Invest 94:2489–2492PubMedCrossRef Reitamo S, Remitz A, Tamai K, Uitto J (1994) Interleukin 10 modulates type 1 collagen and matrix metalloprotease gene expression in cultured human skin fibroblasts. J Clin Invest 94:2489–2492PubMedCrossRef
8.
go back to reference McGaha TL, Bona CA (2002) Role of profibrogenic cytokines secreted by T cells in fibrotic processes in scleroderma. Autoimmun Rev 1:174–181PubMedCrossRef McGaha TL, Bona CA (2002) Role of profibrogenic cytokines secreted by T cells in fibrotic processes in scleroderma. Autoimmun Rev 1:174–181PubMedCrossRef
9.
go back to reference Dziankowska-Bartkowiak B, Zalewska A, Sysa-Jedrzejowska A (2004) Duration of Raynaud’s phenomenon is negatively correlated with serum levels of interleukin 10 (IL-10), soluble receptor of interleukin 2 (sIL2R), and sFas in systemic sclerosis patients. Med Sci Monit 10:202–208 Dziankowska-Bartkowiak B, Zalewska A, Sysa-Jedrzejowska A (2004) Duration of Raynaud’s phenomenon is negatively correlated with serum levels of interleukin 10 (IL-10), soluble receptor of interleukin 2 (sIL2R), and sFas in systemic sclerosis patients. Med Sci Monit 10:202–208
10.
go back to reference Yamamoto T, Eckers B, Kreig T (2001) Effect of interleukin 10 on the gene expression of type 1 collagen, fibronectin and decorin in human skin fibroblasts: differential regulation by transforming growth factor β and monocyte chemoattractant protein-1. Biochem Biophys Res Commun 281:200–205PubMedCrossRef Yamamoto T, Eckers B, Kreig T (2001) Effect of interleukin 10 on the gene expression of type 1 collagen, fibronectin and decorin in human skin fibroblasts: differential regulation by transforming growth factor β and monocyte chemoattractant protein-1. Biochem Biophys Res Commun 281:200–205PubMedCrossRef
11.
go back to reference Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV (1997) An investigation of polymorphisms in the interleukin 10 gene promoter. Eur J Immunogenet 24:1–8PubMed Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV (1997) An investigation of polymorphisms in the interleukin 10 gene promoter. Eur J Immunogenet 24:1–8PubMed
12.
go back to reference Gibson AW, Edberg JC, Wu J, Westendorp RG, Huizinga TW, Kimberly RP (2001) Novel single nucleotide polymorphisms in the distal IL-10 promoter affect IL-10 production and enhance the risk of systemic lupus erythematosus. J Immunol 166:3915–3922PubMed Gibson AW, Edberg JC, Wu J, Westendorp RG, Huizinga TW, Kimberly RP (2001) Novel single nucleotide polymorphisms in the distal IL-10 promoter affect IL-10 production and enhance the risk of systemic lupus erythematosus. J Immunol 166:3915–3922PubMed
13.
go back to reference Westendrop RG, Langermans JA, Huizinga TW, Elouali AH, Verweij CL, Boomsma DI, Vandenbroucke JP (1997) Genetic influence of cytokine production and fatal meningococcal disease. Lancet 349:170–173CrossRef Westendrop RG, Langermans JA, Huizinga TW, Elouali AH, Verweij CL, Boomsma DI, Vandenbroucke JP (1997) Genetic influence of cytokine production and fatal meningococcal disease. Lancet 349:170–173CrossRef
14.
go back to reference Subcommittee for scleroderma criteria of the American Rheumatoid Association Diagnostic, Therapeutic Criteria committee (1980) Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23:581–590CrossRef Subcommittee for scleroderma criteria of the American Rheumatoid Association Diagnostic, Therapeutic Criteria committee (1980) Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23:581–590CrossRef
15.
go back to reference Miller SA, Dykes DD, Polesky HF (1998) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215CrossRef Miller SA, Dykes DD, Polesky HF (1998) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215CrossRef
16.
go back to reference Perrey C, Turner SJ, Pravica V, Howell WM, Hutchinson IV (1997) ARMS-PCR methodologies to determine IL- 10, TNF-α, TNF-β and TGF- β1 gene polymorphisms. Transpl Immunol 7:127–128CrossRef Perrey C, Turner SJ, Pravica V, Howell WM, Hutchinson IV (1997) ARMS-PCR methodologies to determine IL- 10, TNF-α, TNF-β and TGF- β1 gene polymorphisms. Transpl Immunol 7:127–128CrossRef
17.
go back to reference Scala E, Pallotta S, Frezzolini A, Abeni D, Barbieri C, Sampogna F, Depita O, Puddu P, Paganelli R, Russo G (2004) Cytokine and chemokine levels in systemic sclerosis: relationship with cutaneous and internal organ involvement. Clin Exp Immunol 138:540–546PubMedCrossRef Scala E, Pallotta S, Frezzolini A, Abeni D, Barbieri C, Sampogna F, Depita O, Puddu P, Paganelli R, Russo G (2004) Cytokine and chemokine levels in systemic sclerosis: relationship with cutaneous and internal organ involvement. Clin Exp Immunol 138:540–546PubMedCrossRef
18.
go back to reference Beretta L, Cappiello F, Barili M, Scorza R (2007) Proximal interleukin-10 gene polymorphisms in Italian patients with systemic sclerosis. Tissue Antigens 69:305–312PubMedCrossRef Beretta L, Cappiello F, Barili M, Scorza R (2007) Proximal interleukin-10 gene polymorphisms in Italian patients with systemic sclerosis. Tissue Antigens 69:305–312PubMedCrossRef
19.
go back to reference Crilly A, Hamilton J, Clark CJ, Jardine A, Madhok R (2003) Analysis of the 5′ flanking region of the interleukin 10 gene in patients with systemic sclerosis. Rheumatology 42:1295–1298PubMedCrossRef Crilly A, Hamilton J, Clark CJ, Jardine A, Madhok R (2003) Analysis of the 5′ flanking region of the interleukin 10 gene in patients with systemic sclerosis. Rheumatology 42:1295–1298PubMedCrossRef
20.
go back to reference Hudson LL, Rocca KM, Kuwana M, Pandey JP (2005) Interleukin-10 genotypes are associated with systemic sclerosis and influence disease-associated autoimmune responses. Genes Immun 6:274–278PubMedCrossRef Hudson LL, Rocca KM, Kuwana M, Pandey JP (2005) Interleukin-10 genotypes are associated with systemic sclerosis and influence disease-associated autoimmune responses. Genes Immun 6:274–278PubMedCrossRef
21.
go back to reference Ates O, Musellim B, Ongen G, Topal-Sarikaya A (2008) Interleukin-10 and tumor necrosis factor-α gene polymorphisms in tuberculosis. J Clin Immunol 28:232–236PubMedCrossRef Ates O, Musellim B, Ongen G, Topal-Sarikaya A (2008) Interleukin-10 and tumor necrosis factor-α gene polymorphisms in tuberculosis. J Clin Immunol 28:232–236PubMedCrossRef
22.
go back to reference Koss K, Fanning GC, Welsh KI, Jewell DP (2000) Interleukin-10 gene promoter polymorphism in English and Polish healthy controls. Polymerase chain reaction haplotyping using 3′ mismatches in forward and reverse primers. Genes Immun 1:321–324PubMedCrossRef Koss K, Fanning GC, Welsh KI, Jewell DP (2000) Interleukin-10 gene promoter polymorphism in English and Polish healthy controls. Polymerase chain reaction haplotyping using 3′ mismatches in forward and reverse primers. Genes Immun 1:321–324PubMedCrossRef
23.
go back to reference Reynard MP, Turner D, Navarrete CV (2000) Allele frequencies of polymorphisms of the tumor necrosis-alpha, interleukin-10, interferon-gamma and interleukin-2 genes in a North European Caucasoid group from the UK. Eur J Immunogenet 27:241–9PubMedCrossRef Reynard MP, Turner D, Navarrete CV (2000) Allele frequencies of polymorphisms of the tumor necrosis-alpha, interleukin-10, interferon-gamma and interleukin-2 genes in a North European Caucasoid group from the UK. Eur J Immunogenet 27:241–9PubMedCrossRef
24.
go back to reference Hoffmann SC, Stanley EM, Cox ED, DiMercurio BS, Koziol DE, Harlan DM, Kirk AD, Blair PJ (2002) Ethnicity greatly influences cytokine gene polymorphism distribution. Am J Transplant 2:560–567PubMedCrossRef Hoffmann SC, Stanley EM, Cox ED, DiMercurio BS, Koziol DE, Harlan DM, Kirk AD, Blair PJ (2002) Ethnicity greatly influences cytokine gene polymorphism distribution. Am J Transplant 2:560–567PubMedCrossRef
25.
go back to reference Mok CC, Lanchbury JS, Chan DW, Lau CS (1998) Interleukin 10 promoter polymorphisms in southern Chinese patients with systemic lupus erythematosus. Arthritis Rheum 41:1090–1095PubMedCrossRef Mok CC, Lanchbury JS, Chan DW, Lau CS (1998) Interleukin 10 promoter polymorphisms in southern Chinese patients with systemic lupus erythematosus. Arthritis Rheum 41:1090–1095PubMedCrossRef
26.
go back to reference Pyo CW, Hur SS, Kim YK, Choi HB, Hong YS, Kim DW, Kim CC, Kim HK, Kim TG (2003) Polymorphisms of IL-1B, IL-1RN, IL-2, IL-4, IL-6, IL-10, and IFN-γ genes in the Korean population. Hum Immunol 64:979–989PubMedCrossRef Pyo CW, Hur SS, Kim YK, Choi HB, Hong YS, Kim DW, Kim CC, Kim HK, Kim TG (2003) Polymorphisms of IL-1B, IL-1RN, IL-2, IL-4, IL-6, IL-10, and IFN-γ genes in the Korean population. Hum Immunol 64:979–989PubMedCrossRef
27.
go back to reference Ide A, Kawasaki E, Abiru N, Sun F, Takahashi R, Kuwahara H, Fujita N, Kita A, Oshima K, Sakamaki H, Uotani S, Yamasaki H, Yamaguchi Y, Eguchi K (2002) Genetic association between interleukin-10 gene promoter region polymorphisms and type I diabetes age-at-onset. Hum Immunol 63:690–695PubMedCrossRef Ide A, Kawasaki E, Abiru N, Sun F, Takahashi R, Kuwahara H, Fujita N, Kita A, Oshima K, Sakamaki H, Uotani S, Yamasaki H, Yamaguchi Y, Eguchi K (2002) Genetic association between interleukin-10 gene promoter region polymorphisms and type I diabetes age-at-onset. Hum Immunol 63:690–695PubMedCrossRef
Metadata
Title
Association between ‘interleukin’ 10 gene (IL10) polymorphisms and systemic sclerosis with interstitial lung involvement
Authors
Ö. Ates
B. Müsellim
G. Öngen
A. Topal-Sarıkaya
Publication date
01-09-2008
Publisher
Springer-Verlag
Published in
Rheumatology International / Issue 11/2008
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-008-0594-8

Other articles of this Issue 11/2008

Rheumatology International 11/2008 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.