Abstract
BackgroundDiagnostic biomarkers for detecting chronic obstructive pulmonary disease (COPD) in acute coronary syndrome (ACS) patients are not available. SERPINA1, coding for the most potent circulating anti-inflammatory protein in the lung, has been found to be differentially methylated in blood cells from COPD patients. This study aimed to investigate the methylation profile of SERPINA1 in blood cells from ACS patients, with (COPD+) or without COPD (COPD−).MethodsBlood samples were from 115 ACS patients, including 30 COPD+ and 85 COPD− according to lung function phenotype, obtained with spirometry. DNA treated with sodium bisulfite was PCR-amplified at SERPINA1 promoter region. Methylation analysis was carried out by sequencing the PCR products. Lymphocytes count in ACS patients was recorded at hospital admission and discharge.ResultsSERPINA1 was hypermethylated in 24/30 (80%) COPD+ and 48/85 (56.5%) COPD− (p < 0.05). Interestingly, at hospital discharge, lymphocytes count was higher in COPD− patients carrying SERPINA1 hypermethylated (1.98 × 103 ± 0.6 cell/µl) than in COPD− carrying SERPINA1 hypomethylated (1.7 × 103 ± 0.48 cell/µl) (p < 0.05).ConclusionsSERPINA1 is hypermethylated in blood cells from COPD+ patients. COPD− carrying SERPINA1 hypermethylated and high lymphocytes count may be at risk of COPD development. Therefore, SERPINA1 hypermethylation may represent a potential biomarker for predicting COPD development in ACS patients.
Highlights
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that causes obstructedRotondo et al Clin Epigenet (2021) 13:79 long-term prognosis [5]
Only age, respiratory health screening questionnaire (RSHQ), FEV1 and pack-year resulted to be significantly different between chronic obstructive pulmonary disease (COPD)− (n = 85) and COPD+ (n = 30): age 63 ± 9 versus 70 ± 8 years, p = 0.001; RSHQ > 19 29% versus 57%, p = 0.008; FEV1 2.9 ± 0.7 versus 2.0 ± 0.5, p < 0.001; packyear, mean ± SD 34 ± 23 vs 45 ± 38, p < 0.05 in COPD− vs. COPD+, respectively
Since hypomethylated CpG number 1 (CpG-1) and CpG-8 sites have been associated with lower average lung function phenotypes and COPD [26], we investigated the methylation (p < 0.001), age-related changes in SERPINA1 promoter methylation of acute coronary syndrome (ACS) patients were assessed
Summary
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that causes obstructedRotondo et al Clin Epigenet (2021) 13:79 long-term prognosis [5]. Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that causes obstructed. SERPINA1 gene encodes for Alpha-1 antitrypsin (AAT), a blood protease of 52 kDa constitutively released from the hepatocytes [6]. AAT is involved in inflammatory processes [7, 8]. This protein plays a protective role on the healthy cells adjacent to the inflamed tissue where it inhibits different proteases, including the elastase produced by neutrophils [7]. SERPINA1, coding for the most potent circulating anti-inflammatory protein in the lung, has been found to be differentially methylated in blood cells from COPD patients. This study aimed to investigate the methylation profile of SERPINA1 in blood cells from ACS patients, with (COPD+) or without COPD (COPD−)
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