EXTENDED REPORT

Analysis of transforming growth factor ß1 gene polymorphisms in patients with systemic sclerosis

A Crilly¹, J Hamilton², C J Clark³, A Jardine³, R Madhok²

¹ Department of Medicine, 10 Alexandra Parade, Glasgow Royal Infirmary, Glasgow G31 2ER, UK
² Centre for Rheumatic Diseases, Glasgow Royal Infirmary, 84 Castle Street, Glasgow G4 0SF, UK
³ Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT, Glasgow, UK

Correspondence to:
Correspondence to:
Dr R Madhok, Centre for Rheumatic Disease, 84 Castle Street, Glasgow Royal Infirmary, Glasgow G4 0SF, UK;
gcl103{at}clinmed.gla.ac.uk

Objectives: To determine the distribution of transforming growth factor ß1 (TGFß1) genotypes at codon 10 (+869 polymorphism) and codon 25 (+915 polymorphism) in patients with scleroderma (SSc). Differences between diffuse and limited SSc (dSSc and lSSc) were also investigated.

Methods: Patients with lSSc (n=89) and dSSc (n=63) were compared with 147 controls. DNA was isolated from peripheral blood and polymorphisms at codons 10 (C/T) and 25 (G/C) of the TGFß1 gene analysed by polymerase chain reaction and sequence specific oligonucleotide probing.

Results: Significantly more patients with SSc than controls carried allele C at codon 10 (controls v SSc, 38% v 48%, ²=8.2, 1df, p=0.004), OR=1.95 (95% CI 1.16 to 3.27). The difference remained when patients with SSc were split into those with limited or diffuse disease, (controls v dSSc, ²=5, 1df, p=0.02 and controls v lSSc, ²=6, 1df, p=0.013). The patients with SSc had significantly more subjects heterozygous at codon 10 (controls v SSc, ²=45, 1df, p<0.0001). Possession of allele C at codon 10 gave an OR=4.8 (95% CI 2.8 to 8.4). No difference in allele frequency was seen between patients with SSc and controls at codon 25. More patients with SSc than controls carried the GG genotype (controls v SSc, 80% v 88%, ²=7, 2df, p=0.027). Possession of allele G gave an OR=1.7 (95% CI 0.5 to 5.9). There was no difference between diffuse and limited disease at either codon.

Conclusions: These results suggest that patients with SSc are genetically predisposed to high TGFß1 production. These polymorphisms do not, however, explain the difference in the clinical phenotypes of limited and diffuse SSc.

Keywords: systemic sclerosis; TGFß1; polymorphisms

Abbreviations: dSSc, diffuse systemic sclerosis; lSSc, limited systemic sclerosis; OR, odds ratio; PBS, phosphate buffered saline; PCR, polymerase chain reaction; SDS, sodium dodecyl sulphate; SSc, systemic sclerosis; TGFß1, transforming growth factor ß1

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