Analysis of transforming growth factor β1 gene polymorphisms in patients with systemic sclerosis

Objectives: To determine the distribution of transforming growth factor beta1 (TGFbeta1) genotypes at codon 10 (+869 polymorphism) and codon 25 (+915 polymorphism) in patients with scleroderma (SSc). Differences between diffuse and limited SSc (dSSc and ISSc) were also investigated. Methods: Patients with ISSc (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 TGFbeta1 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%, chi(2)=8.2, 1 df, p=0.004), OR=1.95 (95% Cl 1.16 to 3.27). The difference remained when patients with SSc were split into those with limited or diffuse disease, (controls v dSSc, chi(2) =5, 1 df, p=0.02 and controls V ISSc, chi(2) =6, 1 df, p=0.013). The patients with SSc had significantly more subjects heterozygous at codon 10 (controls V SSc, chi(2) = 45, 1 df, p<0.0001). Possession of allele C at codon 10 gave an OR=4.8 (95% Cl 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%, chi(2)=7, 2df, p=0.027). Possession of allele G gave an OR = 1.7 (95% Cl 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 TGF beta 1 production. These polymorphisms do not, however, explain the difference in the clinical phenotypes of limited and diffuse SSc.