A polymorphism within the Transforming Growth Factor β1 gene is associated with ankylosing spondylitis (AS)

Introduction

Genetic factors that predispose individuals to ankylosing spondylitis (AS) are not fully understood. Axial and sacroiliac joint fibrosis are characteristic of AS and the presence of TGFβ1 mRNA in AS sacroiliac joints raised the possibility that this cytokine might be implicated in this fibrosis. We have therefore examined a group of HLA B27 positive AS patients to investigate whether they could be prone to fibrosis based on overproduction of TGFβ1.

Methods

DNA from 132 AS patients, 113 healthy controls from the West of Scotland were compared. DNA covering the G/C polymorphic site at position +915 in the TGFβ1 gene was expanded by PCR and examined using sequence specific primers. Levels of mRNA from stimulated PBMC's from AS patients and controls were analysed using Taqman PCR. Serum TGFβ1 was measured by ELISA on acidified serum.

Results

Although no significant differences in allele frequency was seen between these two populations examination of genotype frequencies showed that the AS patients were more likely to have the GG genotype associated with high TGFβ1 production (78% versus 64%; P < 0.01, OR = 2.0. 95% CI 1.2–3.5). In keeping with this predisposition, the median level of TGFβ1 in serum from AS patients was 6359 pg/ml (range 3266–9587 pg/ml) which was higher (P < 0.02) than the controls (median 4903 pg/ml: range 136–7488 pg/ml). The levels of mRNA from AS patients were higher than controls.

Conclusion

This is the first report of a link with a polymorphic site within the TGFβ1 gene in AS. An increased predisposition to high TGFβ1 production could provide insights into the aetiology to AS. Our data confirm that genes other than B27 may be involved in AS pathogenesis.