Investigation of risk effects of prolidase gene (PEPD) mutations in patients with coronary artery ectasia

Coronary artery ectasia (CAE) is defined as an dilatation of at least one coronary artery 1.5 times or more than the adjacent normal coronary artery segment. Connective tissue diseases are involved in the etiology of CAE. In CAE, weakening of the coronary artery wall connective tissue has been shown to cause positive remodeling. Prolidase is an enzyme involved in collagen metabolism, new matrix formation and cell growth. This is the first comprehensive study to evaluate the variability of prolidase-expressed PEPD gene and serum prolidase level together with clinical phenotype and biochemical parameters as risk factors in CAE patients. PEPD gene was sequenced by MiSeq, a new generation sequencing method, in DNA samples of 76 CAE patients and 76 controls. In the CAE group, hypertension (p=0,006) and hyperlipidemia (p<0,001) were found to be high. In clinical parameters, HbA1c% (p=0,026), triglycerides (p=0,048), ALT (p=0,036), AST (p=0,027) and creatinine (p=0,02) were higher in the CAE group. Serum prolidase levels (p<0,001) and HDL-K (p=0,02) were significantly lower in the CAE group. Serum prolidase levels were lower in the CAE group with PEPD rs17570 G>A variation (GA+AA) genotype (p=0,04) and rs1698070 T>C variation (TC+CC) genotype (p=0,05). Serum prolidase levels (p=0.01) were higher in the control group with genotype in PEPD rs17569 G>A variation (GA+AA). In haplotype analysis, it was observed that rare G allele 17570 and normal G allele rs1061338 together was closely associated with increased CAE risk. In conclusion, it can be said that changes in PEPD gene contribute to the development of CAE.