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

Objectives: To determine the distribution of transforming growth factor β1 (TGFβ1) 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 TGFβ1 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%, χ2=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, χ2=5, 1df, p=0.02 and controls v lSSc, χ2=6, 1df, p=0.013). The patients with SSc had significantly more subjects heterozygous at codon 10 (controls v SSc, χ2=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%, χ2=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