Transforming growth factor-beta gene polymorphisms in sarcoidosis patients with and without fibrosis.
OBJECTIVE
Pulmonary fibrosis develops in approximately 25% of patients with chronic sarcoidosis. Transforming growth factor (TGF)-beta1 plays a central role in fibrosis, and accruing reports address the implication of TGF-beta2 and TGF-beta3 in this process. We determined whether single-nucleotide polymorphisms (SNPs) in the TGF-beta1, TGF-beta2, and TGF-beta3 genes might contribute to pulmonary fibrosis in sarcoidosis patients.


METHODS
A hospital in the Netherlands.


METHODS
Five SNPs per TGF-beta gene were investigated.


METHODS
Patients with either acute/self-remitting sarcoidosis (n = 50) and Löfgren syndrome (n = 46) or chronic disease with fibrosis (n = 24) and without fibrosis (n = 34) were assessed over a 4-year follow-up period. The control subjects included 315 individuals.


RESULTS
Polymorphism frequencies were not discordant between the patients and control subjects. The TGF-beta3 4875 A allele was significantly higher in fibrotic patients (carrier frequency, 0.29) than in patients with acute/self-remitting (0.06) and chronic (0.03) sarcoidosis combined (corrected p = 0.01; odds ratio [OR], 7.9). The TGF-beta3 17369 C allele carrier frequency was significantly higher in fibrotic patients (0.29) compared to acute/self-remitting (0.08) and chronic (0.06) patients combined (corrected p = 0.05; OR, 5.1). Although not significant after correction, the TGF-beta3 15101 G allele carrier frequency was lower in fibrotic patients (0.79) compared to acute/self-remitting (0.94) and chronic (1.00) patients combined (p = 0.02; corrected p = 0.1; OR, 0.15). The TGF-beta2 59941 G allele was more abundant in fibrotic patients (carrier frequency, 0.62) compared to patients with acute/self-remitting (0.41) and chronic sarcoidosis combined (0.28) [p = 0.04; corrected p = 0.2; OR, 2.9]. TGF-beta1 gene polymorphisms were not associated with fibrosis.


CONCLUSIONS
This study is the first to suggest the implication of genetic variation of TGF-beta3 in the predilection for pulmonary fibrosis developing in sarcoidosis patients.
Kruit
Adrian
A
Department of Pulmonology, St. Antonius Hospital, Koekoekslaan 1, 3435 Nieuwegein, The Netherlands.
Grutters
Jan C
JC
Ruven
Henk J T
HJ
van Moorsel
Coline H M
CH
Weiskirchen
Ralf
R
Mengsteab
Senait
S
van den Bosch
Jules M M
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011658:Pulmonary Fibrosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics*; D011859:Radiography; D017565:Sarcoidosis, Pulmonary / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*
D016212:Transforming Growth Factor beta