Polymorphism in ERCC1 confers susceptibility of coronary artery disease and severity of coronary artery atherosclerosis in a Chinese Han population

Abstract

Excision repair cross-complementing 1 (ERCC1) gene encodes ERCC1 protein, which is mainly responsible for the repair of DNA damage in different diseases including coronary artery atherosclerosis by acting as a rate-limiting element in nucleotide excision repair (NER). Using a three-stage case-control study with 3037 coronary artery disease (CAD) patients and 3002 controls, we investigated associations of three single nucleotide polymorphisms (SNPs) with CAD risk and severity of coronary artery atherosclerosis in Chinese Han population. In the discovery set, the variant allele T of rs11615 was significantly associated with higher CAD risk (adjusted OR = 1.27, P = 0.006) and severity of coronary artery atherosclerosis (adjusted OR = 1.54, P = 0.003). These associations were more remarkable in the merged set (adjusted OR = 1.23, P = 8 × 10−6 for CAD risk; adjusted OR = 1.36, P = 4.3 × 10−5 for severity of coronary artery atherosclerosis). And the expression level of ERCC1 was significantly higher in CAD cases than controls. Multiplicative interactions among SNP rs11615, alcohol drinking, history of T2DM, and history of hyperlipidemia could increase 5.06-fold risk of CAD (P = 1.59 × 10−9). No significant association of rs2298881 and rs3212986 with CAD risk was identified. Taken together, SNP rs11615 in ERCC1 gene might confer susceptibility to CAD and severity of coronary atherosclerosis in a Chinese Han population.

Loss of DNA repair mechanisms in cardiac myocytes induce dilated cardiomyopathy

“…There is at least one single nucleotide polymorphism in ERCC1 significantly associated with coronary artery disease (Zhang et al, 2017).…”

“…Increased expression of the DNA repair proteins PCNA, DNA‐PKcs, and APE1 is correlated with left ventricular dysfunction in patients with idiopathic dilated cardiomyopathy, suggesting increased DNA repair activity in diseased cardiac tissue (Bartunek et al, 2002 ). In contrast, reduced expression of numerous DNA repair genes, including ERCC1 , XPA , and ATM , are associated with stable angina and myocardial infarction (Zhang et al, 2017 ). There is at least one single nucleotide polymorphism in ERCC1 significantly associated with coronary artery disease (Zhang et al, 2017 ).…”

“…In contrast, reduced expression of numerous DNA repair genes, including ERCC1 , XPA , and ATM , are associated with stable angina and myocardial infarction (Zhang et al, 2017 ). There is at least one single nucleotide polymorphism in ERCC1 significantly associated with coronary artery disease (Zhang et al, 2017 ).…”

ERCC1 polymorphism and its expression associated with ischemic stroke in Chinese population

“…It was suggested that A allele of the ERCC1 rs3212986 polymorphism might be a risk factor for ischemic stroke. The ERCC1 rs3212986 polymorphism, located on the 3'-UTR of the ERCC1 gene, has been widely studied in previous studies (16,22,23) and might be involved in the potential pathophysiological mechanism in ischemic stroke. ERCC1 rs3212986 polymorphism might affect the DNA repair capacity and interfere with the NER pathway by regulating ERCC1 transcription and translation and/or altering ERCC1 biological activity (24,25).…”

Η Αλληλεπίδραση Μεταξύ Των Μηχανισμών Της Γήρανσης, Της Ρευματοειδούς Αρθρίτιδας Και Των Σχετιζομένων Συννοσηροτήτων

“…Aging has been associated with higher incidence of cardiac dysfunction; however, there are still unanswered questions about the exact molecular mechanisms driving this predisposition. In the past, Ercc1 deletion has been implicated with atherosclerotic cardiovascular disease both in mice (263) and in human patients (264). For this reason, we investigated whether systemic or mesenchymal-specific Ercc1 deletion causes any phenotype in the heart valves of Ercc1 Δ/or ColVI-Cre Ercc1 f/respectively and whether this deletion affects the heart valve disease developed in Tg197 mice.…”