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
|
---|---|
Published in |
Orphanet Journal of Rare Diseases, July 2014
|
DOI | 10.1186/s13023-014-0103-y |
Pubmed ID | |
Authors |
Alberto López-Lera, Olga Pernia, Margarita López-Trascasa, Inmaculada Ibanez de Caceres |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
France | 1 | 25% |
Unknown | 3 | 75% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 2 | 50% |
Members of the public | 2 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Turkey | 1 | <1% |
Unknown | 133 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 9 | 7% |
Student > Bachelor | 4 | 3% |
Student > Ph. D. Student | 4 | 3% |
Professor | 2 | 1% |
Student > Master | 2 | 1% |
Other | 2 | 1% |
Unknown | 111 | 83% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 10 | 7% |
Biochemistry, Genetics and Molecular Biology | 4 | 3% |
Agricultural and Biological Sciences | 3 | 2% |
Veterinary Science and Veterinary Medicine | 2 | 1% |
Immunology and Microbiology | 2 | 1% |
Other | 1 | <1% |
Unknown | 112 | 84% |