TGF-beta1 gene polymorphisms in patients with end-stage heart failure.
BACKGROUND
The regulatory cytokine transforming growth factor (TGF)-beta1 is thought to play a role in atherosclerotic heart disease as well as in idiopathic cardiomyopathy. The production of TGF-beta1 is genetically controlled as polymorphisms in the signaling sequence of the TGF-beta1 gene leucine(10)-->proline and arginine(25)-->proline 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-beta1 codon 10 genotype distribution among patients with IHD, dilated CMP, and controls (p = 0.034; chi(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)-->Pro (codon 10) polymorphism in the TGF-beta1 gene is associated with end-stage heart failure caused by dilated CMP and not with IHD. This observation suggests that TGF-beta1 is involved in the pathogenesis of CMP.
Holweg
C T
CT
Department of Internal Medicine, University Hospital Rotterdam-Dijkzigt, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands. Holweg@inw1.azr.nl
Baan
C C
CC
Niesters
H G
HG
Vantrimpont
P J
PJ
Mulder
P G
PG
Maat
A P
AP
Weimar
W
W
Balk
A H
AH
D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000235:genetics; D003062:Codon / Q000235:genetics; D005260:Female; D005838:Genotype; D006333:Heart Failure / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications / Q000235:genetics; D011110:Polymorphism, Genetic; D012737:Sex Factors; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
D003062:Codon; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1