Abstract 383: A Functional Polymorphism T29C in Transforming Growth Factor Beta 1 Gene is Associated with the Severity of Coronary Artery Disease

Background and Objective: Transforming growth factor beta 1 (TGF-β1) has been previously reported to be involved in pathogenesis of atherosclerosis. However, there are conflicting views about whether TGF-β1 is pro- or anti-atherogenic. The aim of the present study was to establish the contributions of TGF-β1 and its key receptor TGF-β receptor type II (TGFBR2) functional gene polymorphisms to the severity of atherosclerotic coronary artery disease (CAD). Methods and Results: Five hundred and three consecutive patients with angiographically documented CAD were prospectively enrolled in this study. Coronary stenosis severity was assessed by the number of coronary narrowed vessels and the Gensini-score. All patients were genotyped for two TGF-β1 polymorphisms [rs1800471 (+T29C), rs1800470 (+915G/C)] and two TGF BR2 polymorphisms [rs67855385 (-3779A/G), rs764522 (-1444C/G)] by the means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and then confirmed by direct sequencing. No association between TGF-β1 rs1800470 (+915G/C), TGF BR2 rs67855385 (-3779A/G) and rs764522 (-1444C/G) gene polymorphisms and the severity of CAD was observed (P>0.05). TGF-β1 rs1800471 (+T29C) polymorphism was also not significantly associated with severity of CAD in female patients. However, in male CAD patients, polymorphisms at rs1800471 (+T29C) were found to be associated with the severity of CAD. There was a significant difference of the T allele frequency in patients with different numbers of vessels involved (three or more vessels: 49.3%, two vessels: 44.1%, single vessel: 35.8%) (P=0.039). Gensini scores were 34.33 ± 2.23, 32.06 ± 4.7877, and 26.90 ± 3.83 in those with the TT, CT, and CC genotype respectively (P=0.045). By using multiple linear regression, adjusting for other risk factors such as gender, blood pressure, diabetes, history of smoking, and serum lipid levels, the T allele was still positively correlated with the Gensini score and number of vessels involved (β=0.034). Conclusion: Our findings suggest that TGF-β1 T29C gene polymorphism is associated with severity of CAD in Chinese populations.