title: Association between transforming growth factor-beta1 gene C-509T and T869C polymorphisms and rheumatic heart disease.
abstract: BACKGROUND
  Scarring and collagen deposition in the valves and destruction of myocytes may result from the combined effects of a smoldering rheumatic process and a constant trauma to the mitral valve or aortic valve by the turbulent flow in rheumatic heart disease (RHD). Transforming growth factor-beta1 (TGF-beta1) may be responsible for the increased valvular fibrosis and calcification in the pathogenesis of RHD. However, the role of TGF-beta1 genetic variant in RHD has not been studied. This case-controlled study was carried out to investigate the possible relationship between the TGF-beta1 gene C-509T and T869C polymorphisms and RHD among the Chinese population in Taiwan.
  
  
  METHODS
  A group of 115 patients with RHD documented by using echocardiography and 100 age- and sex-matched healthy control patients were studied. TGF-beta1 gene C-509T and T869C polymorphisms were identified with polymerase chain reaction-based restriction analysis.
  
  
  RESULTS
  A significant difference was seen in the distribution of genotypes between patients with RHD and control patients for either TGF-beta1 C-509T polymorphism (P <.0001) or T869C polymorphism (P <.0001). The frequency of TGF-beta1 C-509T CC genotype was lower in the RHD group than in the control group (chi2 = 19.05, P <.0001), which suggests that this genotype may confer protective effects against RHD. A significant difference was seen in the distribution of allelic frequency between patients with RHD and control patients for TGF-beta1 T869C polymorphism (P =.04). The odds ratio (OR) for risk of RHD associated with TGF-beta1 T869C T allele was 1.49 (95% CI, 1.02-2.19). Further categorization of patients with RHD into mitral valve disease and combined valve disease subgroups revealed no statistical difference in these gene polymorphisms when compared with the 2 subgroups.
  
  
  CONCLUSIONS
  Patients with RHD have a lower frequency of TGF-beta1 C-509T CC genotype and a higher frequency of T869C T allele, which supports a role for the TGF-beta1 gene C-509T and T869C polymorphisms in determining the risk/protection of RHD in Taiwan Chinese patients.
authors.affiliation: Division of Cardiology, Department of Medicine, China Medical University Hospital, Taichung, Taiwan. chou.hsieh@msa.hinet.net
authors.forename: Hsiang-Tai
authors.initials: HT
authors.lastname: Chou
authors.forename: Chien-Hsiun
authors.initials: CH
authors.lastname: Chen
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Tsai
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D005260:Female; D005828:Genetics, Population; D005838:Genotype; D006349:Heart Valve Diseases / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000208:ethnology / Q000235:genetics; D008946:Mitral Valve Stenosis / Q000000981:diagnostic imaging / Q000208:ethnology / Q000235:genetics*; D011110:Polymorphism, Genetic; D012214:Rheumatic Heart Disease / Q000145:classification / Q000208:ethnology / Q000235:genetics*; D012720:Severity of Illness Index; D013624:Taiwan; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D014463:Ultrasonography
chemical_list: C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1