Investigation of clinical phenotypic associations of functional variations in tgf β genes in atherosclerotic coronary artery ectasia patients

Coronary artery ectasia is diagnosed angiographically and characterized by the enlargement of a coronary artery segment to 1.5 times or more compared to the adjacent coronary artery segment. It can be seen in one or more coronary arteries, as well as localized or diffuse in the same coronary artery. The frequency varies from 1.2 to 4.9%. Fifty-percent of all coronary ectasias have atherosclerotic bacground. Atherosclerotic changes that occur in the tunica intima deteriorate elastic composition of tunica media. These changes lead to arterial remodeling and the process results in coronary artery ectasia. TGF β is a cytokine that plays an important role in inflammatory processes. It has been shown that TGF β gene variants and plasma levels have an association with various disease groups. TGF β has anti-inflammatory properties that has shown to prevent atherosclerosis. Because of this property, it is known as a protective cytokine. Cystatin C is an inhibitor of cysteine proteinases which are extracellular matrix destructive enzymes. It is believed to prevent coronary artery ectasia as it prevents the destruction of the extracellular matrix. In our study, we aimed to investigate distrubution of TGF β1 rs1800469 and rs1800470 gene polymorphisms, serum TGF β1 and serum cystatin c levels in patients with coronary artery ectasia.. To best of our knowlodge this is the first study that investigate the role of TGF β gene variants in coronary ectasia. Fifty-six patients with coronary ectasia patients were included in our study whereas 44 patients with normal coronary arteries constitute the control group. TGF β1 genotypes were determined using polymerase chain reaction, restriction fragment length polymorphism, and agarose gel electrophoresis techniques; serum TGF β and serum cystatin C levels determined by Elisa method. There was no difference in the genotype and allele distributions of TGF β1 rs1800469 and rs1800470 polymorphisms between the coronary artery ectasia group and the control group (p>0,05). Serum TGF β level was significantly lower in patients with coronary artery ectasia compared to the control group (p=0,012). There was no significant difference in serum cystatin C levels between the coronary artery ectasia group and the control group (p>0,05). The presence of male gender (p = 0.002), hypertension (p = 0.042) and hyperlipidemia (p = 0.003) was found to be more frequent in coronary artery ectasia patients compared to the control group. When the coronary artery ectasia group examined in itself, low serum TGF β levels found in individuals carrying the normal homozygous AA genotype in the TGF β1 rs1800470 gene variants compared to individuals carrying the G allele (GG + AG genotype) (p=0,012). Regression analysis confirmed that serum TGF β levels, male sex, and hyperlipidemia increased the risk of developing coronary artery ectasia. In conclusion, there was no difference in genotype and allelic distribution of TGF β1 rs1800469 and rs1800470 gene variants between the coronary artery ectasia group and the control group in our study. In the coronary artery ectasia group, serum TGF β level was found to be lower than the control group. Serum cystatin C levels were similar between the groups. Hypertension, hyperlipemia and male sex were more frequent in coronary ectasia group as expected.