SERPINA1 Gene Promoter Is Differentially Methylated in Peripheral Blood Mononuclear Cells of Pregnant Women

Abstract

SERine Protein INhibitor-A1 (SERPINA1) is an inducible blood cell gene coding for alpha1-antitrypsin (AAT), a plasma protease inhibitor whose circulating levels are raised during inflammation, infection and advanced pregnancy. DNA methylation has been suggested to play a role in SERPINA1 gene expression regulation in peripheral blood mononuclear cells (PBMCs). The methylation status of SERPINA1 in PBMCs is unknown. The aim of this study was to evaluate the methylation profile of the SERPINA1 promoter in PBMC. To this purpose PBMCs and serum were collected from healthy subjects (HS) (n = 75), including blood donors (BD) (n = 25), pregnant women at early pregnancy (EP) (n = 25), i.e., within the first trimester, and pregnant women at late pregnancy (LP) (n = 25), i.e., at the third trimester. DNA from PBMCs was treated with sodium bisulfite and PCR amplified for SERPINA1 gene promoter, followed by sequencing analyses. AAT serum levels were determined by ELISA test. SERPINA1 was found hypermethylated in 58.7% of HS. The prevalence of SERPINA1 hypermethylation was significantly higher in BD (68%) and EP (88%) than in LP (20%) (p < 0.01). The median serum AAT concentration was 1.07, 0.63, and 3.15 mg/ml in BD, EP, and LP, respectively (p < 0.05, BD and EP vs LP). This study indicates, for the first time, that SERPINA1 gene promoter is differentially methylated in PBMCs from HS. Likely, modulation of the methylation may be a novel epigenetic regulator mechanism of AAT expression in the PBMC of HS. Therefore, SERPINA1 gene promoter methylation may represent an epigenetic biomarker of PBMCs in healthy subjects.

MicroRNAs Modulate Signaling Pathways in Osteogenic Differentiation of Mesenchymal Stem Cells

“…HDAC is a family of key epigenetic factors that regulates the expression of genes in concert with DNA methylation and miRNA expression [ 120 , 121 , 122 , 123 , 124 ]. In the TGF-β signaling pathway, the HDAC4/5 complex binds the nuclear phosphorylated R-SMAD SMAD2/3 to repress RUNX2 expression, resulting in osteoblast differentiation inhibition [ 125 ].…”

Association between oncogenic human papillomavirus type 16 and Killian polyp

“…Statistical analyses were performed using the GraphPad Prism for Windows (version 6.0, GraphPad, California, USA) [48,49]. For mRNA, fold change was calculated by the 2 -ΔΔCt method and represented in Log 2 scale, using HPV-negative samples as controls [31].…”

Methylation of SERPINA1 gene promoter may predict chronic obstructive pulmonary disease in patients affected by acute coronary syndrome

“…SERPINA1 is also an inducible gene upon activating its inflammation-responsive promoter in hepatocytes, monocytes and macrophages [ 7 , 16 , 17 ]. High levels of circulating AAT, fourfold to sixfold higher than baseline levels, are present during the course of inflammation, infections and late pregnancy [ 18 – 21 ].…”

“…In a recent study we have performed a comprehensive assessment of SERPINA1 gene promoter methylation profile in peripheral blood mononuclear cells (PBMCs) from healthy subjects [ 21 ]. We showed that SERPINA1 gene promoter is hypermethylated in healthy individuals, such as blood donors, but hypomethylated in pregnant women at the third trimester of pregnancy.…”

“…We showed that SERPINA1 gene promoter is hypermethylated in healthy individuals, such as blood donors, but hypomethylated in pregnant women at the third trimester of pregnancy. These findings suggest that SERPINA1 gene is normally silenced in blood cells of healthy individuals, but it is induced under emergency conditions, such as late pregnancy, when women are highly exposed to the risk of inflammations and infections [ 21 ].…”