TGF-beta1 gene polymorphisms in patients with end-stage heart failure.

Abstract

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.

• Authors: C T Holweg, C C Baan, H G Niesters, P J Vantrimpont, P G Mulder, A P Maat, W Weimar, A H Balk
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 20 Issue 9 Pg. 979-84 (Sep 2001) ISSN: 1053-2498 [Print] United States
• PMID: 11557193 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Codon
• TGFB1 protein, human
• Transforming Growth Factor beta
• Transforming Growth Factor beta1

Topics

• Adult
• Cardiomyopathy, Dilated (complications, genetics)
• Codon (genetics)
• Female
• Genotype
• Heart Failure (genetics)
• Humans
• Male
• Middle Aged
• Myocardial Ischemia (complications, genetics)
• Polymorphism, Genetic
• Sex Factors
• Transforming Growth Factor beta (genetics)
• Transforming Growth Factor beta1