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.
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: Thomas Doetschman; Joey V Barnett; Raymond B Runyan; Todd D Camenisch; Ronald L Heimark; Henk L Granzier; Simon J Conway; Mohamad Azhar Journal: Cell Tissue Res Date: 2011-09-28 Impact factor: 5.249