0
Original Research: SARCOIDOSIS |

Transforming Growth Factor-β Gene Polymorphisms in Sarcoidosis Patients With and Without Fibrosis*

Adrian Kruit, MSc; Jan C. Grutters, MD, PhD; Henk J. T. Ruven, PhD; Coline H. M. van Moorsel, PhD; Ralf Weiskirchen, PhD; Senait Mengsteab, BSc; Jules M. M. van den Bosch, MD, PhD, FCCP
Author and Funding Information

*From the Heart Lung Centre Utrecht, St. Antonius Hospital, Departments of Pulmonology (Mr. Kruit, and Drs. Grutters and van den Bosch), and Clinical Chemistry (Drs. Ruven and van Moorsel), Nieuwegein, the Netherlands; and Institute of Clinical Chemistry and Pathobiochemistry (Dr. Weiskirchen and Ms. Mengsteab), RWTH-University Hospital, Aachen, Germany.

Correspondence to: Jules M. M. van den Bosch, MD, PhD, Department of Pulmonology, St. Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, the Netherlands; e-mail: j.vandenbosch@antonius.net



Chest. 2006;129(6):1584-1591. doi:10.1378/chest.129.6.1584
Text Size: A A A
Published online

Study objectives: Pulmonary fibrosis develops in approximately 25% of patients with chronic sarcoidosis. Transforming growth factor (TGF)-β1 plays a central role in fibrosis, and accruing reports address the implication of TGF-β2 and TGF-β3 in this process. We determined whether single-nucleotide polymorphisms (SNPs) in the TGF-β1, TGF-β2, and TGF-β3 genes might contribute to pulmonary fibrosis in sarcoidosis patients.

Setting: A hospital in the Netherlands.

Design: Five SNPs per TGF-β gene were investigated.

Patients and control subjects: 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.

Measurements and results: Polymorphism frequencies were not discordant between the patients and control subjects. The TGF-β3 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-β3 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-β3 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-β2 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-β1 gene polymorphisms were not associated with fibrosis.

Conclusions: This study is the first to suggest the implication of genetic variation of TGF-β3 in the predilection for pulmonary fibrosis developing in sarcoidosis patients.

Figures in this Article

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543