FAILING HEART—BASIC SCIENCE
TGF-1 Gene Polymorphisms in
Patients With End-Stage
Heart Failure
C. T. J. Holweg, BSc,
a
C. C. Baan, PhD,
a
H. G. M. Niesters, PhD,
b
P. J. M. J. Vantrimpont, MD,
c
P. G. H. Mulder, PhD,
d
A. P. W. M. Maat, MD,
e
W. Weimar, MD, PhD,
a
and
A. H. M. M. Balk, MD, PhD
e
Background: The regulatory cytokine transforming growth factor (TGF)-1 is thought
to play a role in atherosclerotic heart disease as well as in idiopathic cardiomyopathy.
The production of TGF-1 is genetically controlled as polymorphisms in the signaling
sequence of the TGF-1 gene leucine
10
3proline and arginine
25
3proline are involved
in the regulation of the protein production level. We investigated whether these
polymorphisms are associated with end-stage heart failure caused by dilated
cardiomyopathy (CMP) or ischemic heart disease (IHD).
Methods: We determined polymorphisms using sequence specific oligonucleotide probing
(SSOP) in genomic DNA samples from heart transplant recipients (n = 253) and controls
(n = 94). Indications for transplantation were dilated CMP (n = 109) and IHD (n = 144).
Results: We found a difference in TGF-1 codon 10 genotype distribution among
patients with IHD, dilated CMP, and controls (p = 0.034;
2
test). Patients with dilated
CMP differed from patients with IHD (p = 0.044) and healthy controls (0.017). The
genotype distribution between patients with IHD and controls was comparable. For
codon 25, we found no difference in genotype distribution.
Conclusions: The Leu
10
3 Pro (codon 10) polymorphism in the TGF-1 gene is
associated with end-stage heart failure caused by dilated CMP and not with IHD. This
observation suggests that TGF-1 is involved in the pathogenesis of CMP. J Heart
Lung Transplant 2001;20:979–984.
The involvement of cytokines in the pathogenesis
of cardiovascular disease causing heart failure has
been extensively demonstrated. Transforming
growth factor–1 (TGF-1), a regulatory cytokine
produced by many cell types, has been studied in
relation to the pathogenesis of coronary artery
disease. Both anti-atherogenic and pro-atherogenic
activities of TGF-1 have been reported.
1–4
Trans-
forming growth factor–1 inhibits the proliferation
of many cells, including smooth muscle cells, endo-
From the Departments of
a
Internal Medicine,
b
Diagnostic Insti-
tute of Molecular Biology,
c
Cardiology and
e
Thoracic Surgery,
University Hospital Rotterdam-Dijkzigt; and
d
Epidemiology
and Biostatistics, Erasmus University Rotterdam, Rotterdam,
The Netherlands.
Submitted August 4, 2000; accepted March 27, 2001.
Reprint requests: Cecile Holweg, University Hospital Rotter-
dam-Dijkzigt, Department of Internal Medicine, Room Bd293,
Dr. Molewaterplein 40, 3015 GD Rotterdam, The Nether-
lands. Telephone: 31-10-4635420. Fax: 31-10-4635430. E-mail:
Holweg@inw1.azr.nl.
Copyright © 2001 by the International Society for Heart and
Lung Transplantation.
1053-2498/01/$–see front matter PII S1053-2498(01)00296-0
979