title: Polymorphisms of TGFβ-1 and TGFBR2 in relation to coronary artery disease in a Chinese population.
abstract: OBJECTIVE
  TGF-β1 has been previously reported to be involved in the pathogenesis of atherosclerosis. The aim of the present study was to assess whether functional gene polymorphisms of TGF-β1 and its key receptor TGF-β receptor type II (TGFBR2) contribute as risk factors to the onset and severity of atherosclerotic coronary artery disease (CAD).
  
  
  METHODS
  A total of 605 patients who underwent angiography for suspected CAD were prospectively recruited to this study. Coronary stenosis severity was assessed by the number of narrowed coronary vessels and the Gensini score. Among them, 502 patients had documented CAD, and 103 patients without documented CAD served as non-CAD controls. All patients were genotyped for one TGF-β1 polymorphism (rs1800470 (+T29C)) and two TGFBR2 polymorphisms (rs6785385 (-3779A/G), rs764522 (-1444C/G)) by polymerase chain reaction-restriction fragment length polymorphism and confirmed by direct sequencing.
  
  
  RESULTS
  No significant difference in the frequency for either polymorphism was found between CAD and control patients. Neither TGFBR2 rs6785385 (-3779A/G) nor rs764522 (-1444C/G) gene polymorphisms were associated with the severity of CAD (P>0.05). In male CAD patients, polymorphisms at TGF-β1 rs1800470 (+T29C) were, however, associated with the severity of CAD. The T allele frequency was significantly and positively correlated with the number of narrowed coronary arteries (three or more vessels: 49.3%, two vessels: 44.1%, one vessel: 36.9%) (P=0.039). Gensini scores in patients with the TT, CT, and CC genotype were 34.33±2.23, 32.06±4.79, and 26.90±3.83, respectively (P<0.05). In multiple linear regression analysis, the T allele of TGF-β1 polymorphism was independently correlated with the Gensini score (β=0.131).
  
  
  CONCLUSIONS
  TGF-β1 T29C gene polymorphism may be associated with severity of CAD in male patients. TGFBR2 polymorphisms may not determine the genetic susceptibility to CAD.
authors.affiliation: Laboratory of Cardiovascular Disease, China; Department of Cardiology, Taizhou Hospital, Wenzhou Medical University, Zhejiang Province 317000, China.
authors.forename: Minjun
authors.initials: M
authors.lastname: Yang
authors.affiliation: Enze Medical Research Center, Taizhou, Zhejiang Province 317000, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Laboratory of Cardiovascular Disease, China; Zhejiang Hospital, Zhejiang Province 317000, China.
authors.forename: Lijiang
authors.initials: L
authors.lastname: Tang
authors.affiliation: Laboratory of Cardiovascular Disease, China; Department of Cardiology, Taizhou Hospital, Wenzhou Medical University, Zhejiang Province 317000, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Laboratory of Cardiovascular Disease, China; Department of Cardiology, Taizhou Hospital, Wenzhou Medical University, Zhejiang Province 317000, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Vascular Center, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Baohui
authors.initials: B
authors.lastname: Xu
authors.affiliation: Laboratory of Cardiovascular Disease, China; Department of Cardiology, Taizhou Hospital, Wenzhou Medical University, Zhejiang Province 317000, China. Electronic address: Jiangjj@enzemed.com.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Laboratory of Cardiovascular Disease, China; Department of Cardiology, Taizhou Hospital, Wenzhou Medical University, Zhejiang Province 317000, China; Enze Medical Research Center, Taizhou, Zhejiang Province 317000, China. Electronic address: zjxiaofengchen@hotmail.com.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Chen
mesh_terms: D000368:Aged; D000483:Alleles; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D015415:Biomarkers; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: Atherosclerosis; Coronary artery disease; Gene mutations; Transforming growth factor beta