Background and aim: 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).
Design and 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).
Conclusion: 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.
Keywords: Atherosclerosis; Coronary artery disease; Gene mutations; Transforming growth factor beta.
Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.