Transforming Growth Factor Beta (TGFβ) Gene Polymorphisms in Different Phenotypes of Sarcoidosis

Study objective: The etiology of sarcoidosis is unclear. Single nucleotide polymorphisms (SNPs) in transforming growth factor beta (TGFβ)-2 and -3 were reported to be associated with the development of lung fibrosis in patients with sarcoidosis.

Setting: University Hospital Bonn, Germany

Design: One SNP in TGFβ-2 (rs1891467) and one SNP in TGFβ-3 (rs3917200) which were reported to be associated with lung fibrosis in sarcoidosis patients were investigated by real-time-polymerase chain reaction (PCR).

Patients and control subjects: 296 patients with sarcoidosis (acute/self remitting=70, chronic n=168, acute/chronic=58, fibrosis n=34) were investigated. The genotype frequencies were compared among the sarcoidosis groups as well as to 377 healthy controls.

Measurements and results: All polymorphisms were in Hardy-Weinberg-Equilibrium. None of the examined SNPs was significantly associated with lung fibrosis in patients with sarcoidosis, though we could observe a trend in both SNPs towards the development of lung fibrosis (rs1891467p=0.06, rs3917200p=0.08). However, we found a significant association with the mutant G-allele in rs1891467 in TGFβ-2 and an acute/self remitting course of sarcoidosis (p=0.001) compared to a chronic course.

Conclusion: We did not find any significant evidence that rs1891467 and rs3917200 are involved in the development of lung fibrosis in sarcoidosis. However, carriers of the mutant G-allele in rs1891467 seem to be protected of developing a chronic course. This study is the first in sarcoidosis patients to suggest a genetic implication of TGFβ-2 as a protective factor in the course of sarcoidosis.