SERPINA1 Gene Promoter Is Differentially Methylated in Peripheral Blood Mononuclear Cells of Pregnant Women
SERPINA1 Gene Promoter Is Differentially Methylated in Peripheral Blood Mononuclear Cells of Pregnant Women
复制标题
孕妇外周血单个核细胞中SERPINA1基因启动子差异甲基化
DOI：
10.3389/fcell.2020.550543
复制
发表时间：
2020-09-03
影响因子：
5.5
通讯作者：
Martini, Fernanda
中科院分区：
文献类型：
--
作者：
Rotondo, John Charles;Oton-Gonzalez, Lucia;Martini, Fernanda
丝氨酸蛋白抑制剂-A1（SERPINA 1）是一种可诱导的血细胞基因，编码α 1-抗胰蛋白酶（AAT），一种血浆蛋白酶抑制剂，其循环水平在炎症，感染和晚期妊娠期间升高。DNA甲基化在外周血单个核细胞（PBMC）中SERPINA 1基因表达调控中起重要作用。PBMC中SERPINA 1的甲基化状态尚不清楚。本研究的目的是评估PBMC中SERPINA 1启动子的甲基化谱。为此目的，从健康受试者（HS）（n= 75）收集PBMC和血清，包括献血者（BD）（n= 25）、妊娠早期的孕妇（EP）（n= 25），即，妊娠早期和妊娠晚期（LP）的孕妇（n= 25），即，在妊娠晚期。用亚硫酸氢钠处理PBMC DNA，PCR扩增SERPINA 1基因启动子，然后进行测序分析。ELISA法检测血清AAT水平，58.7%的HS患者血清SERPINA 1高甲基化。BD和EP的SERPINA 1基因甲基化率分别为68%和88%，均显著高于LP的20%（P< 0.01）。BD、EP和LP的中位血清AAT浓度分别为1.07、0.63和3.15 mg/ml（p< 0.05，BD和EP vs LP）。这项研究表明，第一次，SERPINA 1基因启动子差异甲基化的PBMC从HS。可能的是，甲基化的调节可能是HS PBMC中AAT表达的一种新的表观遗传调节机制。因此，SERPINA 1基因启动子甲基化可能代表健康受试者PBMC的表观遗传生物标志物。
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 ofSERPINA1in 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.SERPINA1was found hypermethylated in 58.7% of HS. The prevalence ofSERPINA1hypermethylation 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.