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Rheumatology Advance Access published online on July 16, 2003
Rheumatology, doi:10.1093/rheumatology/keg420
Rheumatology © British Society for Rheumatology 2003; all rights reserved
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© 2003 Rheumatology 42 © British Society for Rheumatology 2003; all rights reserved

Original Papers

Analysis of the 5' flanking region of the interleukin 10 gene in patients with systemic sclerosis

A. Crilly 1, J. Hamilton 2, C. J. Clark 3, A. Jardine 3, and R. Madhok 2*

1 Department of Medicine, 10 Alexandra Parade, Glasgow Royal Infirmary, Glasgow, UK
2 Centre for Rheumatic Diseases, Glasgow Royal Infirmary, Glasgow, UK
3 Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK

* Corresponding author. E-mail: gcl103{at}clinmed.gla.ac.uk.

Received 23 December 2002 ; accepted 22 April 2003

Abstract

Objectives. Fibrosis, a feature of systemic sclerosis (SSc), is more severe in the diffuse compared with the limited disease variant. Interleukin 10 (IL-10) is an anti-inflammatory cytokine which reduces type 1 collagen mRNA levels in human fibroblasts. The 5' flanking region of the IL-10 gene is highly polymorphic, with three single base pair substitutions at position -1082(G/A), -819(C/T) and -592(C/A), which results in differential IL-10 production. The GCC/GCC genotype is associated with high IL-10 production while the ATA/ATA genotype with low production. We postulated that there would be a difference in IL-10 polymorphisms in patients with limited (lSSc) and diffuse (dSSc) disease.

Methods. Patients with limited (lSSc, n = 89) or diffuse (dSSc, n = 51) disease plus controls (n = 94) were recruited. DNA was isolated from peripheral blood and polymorphisms analysed using amplification refractory mutation system (ARMS) polymerase chain reaction (PCR).

Results. dSSc patients were less likely to carry the genotype indicative of high IL-10 production when compared with controls (controls vs dSSc; 29 vs 4%, {chi}2 = 15.7, 5 df, P = 0.005) and lSSc patients (lSSc vs dSSc; 21 vs 4%, {chi}2 = 17.5, 5 df, P = 0.002). There was no difference between control and lSSc patients. While there was no difference between controls and lSSc haplotypes, the GCC haplotype distribution did differ significantly between controls and dSSc patients (controls vs dSSc; 54 vs 36%, {chi}2 = 11.2, 2 df, P = 0.001). A significant difference was also observed between lSSc and dSSc haplotype distribution (lSSc vs dSSc; 48 vs 36%, {chi}2 = 13.5, 2 df, P < 0.001).

Conclusion. We demonstrate that IL-10 genotypes associated with high IL-10 production are under-represented in dSSc. This may have implications in the disease pathology.

Key words: Systemic sclerosis, Polymorphisms, Interleukin 10.
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