title: Expression of the SERPING1 gene is not regulated by promoter hypermethylation in peripheral blood mononuclear cells from patients with hereditary angioedema due to C1-inhibitor deficiency.
abstract: SERPING1 mutations causing Hereditary Angioedema type I (HAE-I) due to C1-Inhibitor (C1-INH) deficiency display a dominant-negative effect usually resulting in protein levels far below the expected 50%. To further investigate mechanisms for its reduced expression, we analyzed the promoter DNA methylation status of SERPING1 and its influence on C1-INH expression. Global epigenetic reactivation correlated with C1-INH mRNA synthesis and protein secretion in Huh7 hepatoma cells. However, PBMCs extracted from controls, HAE-I and HAE-II patients presented identical methylation status of the SERPING1 promoter when analyzed by bisulphite sequencing; the proximal CpG island (exon 2) is constitutively unmethylated, while the most distant one (5.7Kb upstream the transcriptional start site) is fully methylated. These results correlate with the methylation profile observed in Huh7 cells and indicate that there is not a direct epigenetic regulation of C1-INH expression in PBMCs specific for each HAE type. Other indirect modes of epigenetic regulation cannot be excluded.
authors: Alberto
authors: A
authors: López-Lera
authors: Olga
authors: O
authors: Pernia
authors: Margarita
authors: M
authors: López-Trascasa
authors: Inmaculada
authors: I
authors: Ibanez de Caceres
mesh_terms: D054179:Angioedemas, Hereditary / Q000097:blood / Q000235:genetics*; D003174:Complement C1 Inactivator Proteins / Q000235:genetics* / Q000378:metabolism; D050718:Complement C1 Inhibitor Protein; D018899:CpG Islands; D019175:DNA Methylation; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D012333:RNA, Messenger; C469952:SERPING1 protein, human