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DNA binding protein 1 (DDB1) has an accessory role in nucleotide excision repair (NER). It forms the large subunit of the heterodimeric DNA damage binding complex which binds to UV induced damaged DNA. Other cellular functions include regulation of DNA replication and chromatin remodelling. Defective activity is associated with Xeroderma Pigmentosum, an autosomal recessive disorder characterized by photosensitivity and early onset of carcinomas. We aimed to identify a previously unreported differential DDB1 gene expression between patients with stable angina (SA) and controls in addition to a correlation with plaque morphology, hence proposing a potential target for modulating atherosclerotic plaque.
47 patients with SA undergoing frequency domain optical coherence tomography-guided (FD-OCT) percutaneous coronary intervention (PCI) and 33 age/sex matched controls were recruited. A custom microarray was used to perform quantitative reverse transcription polymerase chain reaction (qRT-PCR) from purified isolated ribonucleic acid. Patients with diabetes, left ventricular impairment, bleeding diathesis, renal impairment, antiplatelet intolerance, malignancy, active inflammatory disease and prior coronary revascularisation were excluded.
DDB1 was significantly down-regulated in SA versus control (p<0.001) and a positive correlation was found between qRT-PCR cycle threshold (Ct) and lipid arc (Spearman rho=0.452, p=0.006). Ct is inversely proportional to mRNA transcripts indicating lower DDB1 expression with a higher lipid arc.
DDB1 gene expression was down-regulated in SA compared with controls. Lower expression correlated with a higher lipid arc suggesting lower NER activity may contribute to larger lipid debris and necrotic cores in atherogenesis.
OTHER: Genomics / Proteomics