Rheumatology Advance Access originally published online on July 16, 2003
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Rheumatology 2003; 42: 1295-1298
© 2003 British Society for Rheumatology
Analysis of the 5' flanking region of the interleukin 10 gene in patients with systemic sclerosis
Department of Medicine, 10 Alexandra Parade, Glasgow Royal Infirmary, Glasgow G31 2ER, 1Centre for Rheumatic Diseases, Glasgow Royal Infirmary, 84 Castle Street, Glasgow G4 OSF and 2Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT, UK.
Correspondence to:
R. Madhok, Centre for Rheumatic Disease, 84 Castle Street, Glasgow Royal Infirmary, Glasgow G4 OSF, UK. E-mail: gcl103{at}clinmed.gla.ac.uk
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%, 
2 = 15.7, 5 df, P = 0.005) and lSSc patients (lSSc vs dSSc; 21 vs 4%, 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%, 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%, 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.