title: A novel association between TGFb1 and ADAMTS4 in coronary artery disease: A new potential mechanism in the progression of atherosclerosis and diabetes.
abstract: OBJECTIVE
  Coronary artery disease is characterized by atherosclerosis in the vessel wall. Recently, it has been thought that increasing LDL-binding capacity of subendothelial proteoglycan fragments that are formed by protease activity can be responsible for the initiation of atherosclerosis. ADAMTS4 is a member of the versican-degrading proteinases. In vitro studies demonstrated that TGFb inhibits the expression of ADAMTS4 in macrophages. In this study, we aimed to investigate the role and association between TGFb1 and ADAMTS4 in coronary artery disease.
  
  
  METHODS
  A total of 84 cases with atheroma plaque and 72 controls without plaque were analyzed. The severity of disease was determined by Gensini score. TGFb1 gene polymorphisms were genotyped by the PCR-RFLP method. TGFb1 and ADAMTS4 serum levels were measured by ELISA method. Statistical analyses of genotypes and their relationship with serum levels were performed by chi-square, student t test and ANOVA.
  
  
  RESULTS
  ADAMTS4 levels were higher in cases compared with controls (p<0.05). In the patient group, ADAMTS4 levels were higher than in controls and correlated with TGFb1 serum levels (r=0.29; p<0.05) and severity of disease (r=0.20; p<0.05). The TGFb1 gene CCA haplotype was associated with 3.3-fold increase in coronary artery disease (OR=3.26 95% CI 1.22-8.68; p<0.05). Unexpectedly, ADAMTS4 serum levels were also higher in diabetic cases (p=0.05).
  
  
  CONCLUSIONS
  This study has demonstrated that ADAMTS4 may be responsible for the pathogenesis of atherosclerosis. This is the first report about the association between ADAMTS4 and TGFb1 serum levels in the progression of atherosclerosis in CAD. Furthermore, it is seen that TGFb1 haplotype can cause a genetic susceptibility to CAD in the Turkish population. To our knowledge, this is also the first report suggesting higher serum ADAMTS4 levels in diabetic patients.
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Celal Bayar University; Manisa Turkey. safiyeustunoglu@gmail.com.
authors.forename: Safiye
authors.initials: S
authors.lastname: Uluçay
authors.forename: Fethi Sırrı
authors.initials: FS
authors.lastname: Çam
authors.forename: Muhammed Burak
authors.initials: MB
authors.lastname: Batır
authors.forename: Recep
authors.initials: R
authors.lastname: Sütçü
authors.forename: Özgür
authors.initials: Ö
authors.lastname: Bayturan
authors.forename: Kadir
authors.initials: K
authors.lastname: Demircan
mesh_terms: D051722:ADAM Proteins / Q000097:blood* / Q000235:genetics; D000071121:ADAMTS4 Protein; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011348:Procollagen N-Endopeptidase / Q000097:blood* / Q000235:genetics; D012372:ROC Curve; D012720:Severity of Illness Index; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000235:genetics*
chemical_list: D015415:Biomarkers; D053773:Transforming Growth Factor beta1; D051722:ADAM Proteins; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human