Bone morphogenetic protein receptor 2 in patients with idiopathic portal hypertension
Andrea De Gottardi
Hepatic Hemodynamic Laboratory, Liver Unit, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
Hepatology, Department of Clinical Research, University of Berne, Switzerland
The authors share the first authorship.
Search for more papers by this authorSusana Seijo
Hepatic Hemodynamic Laboratory, Liver Unit, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
The authors share the first authorship.
Search for more papers by this authorMontserrat Milá
Biochemical and Molecular Genetics Department, Hospital Clínic, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III, Spain
Search for more papers by this authorM. Isabel Alvarez
CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III, Spain
Search for more papers by this authorMiquel Bruguera
Hepatic Hemodynamic Laboratory, Liver Unit, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
Search for more papers by this authorJuan G. Abraldes
Hepatic Hemodynamic Laboratory, Liver Unit, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
Search for more papers by this authorJaime Bosch
Hepatic Hemodynamic Laboratory, Liver Unit, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
Search for more papers by this authorCorresponding Author
Juan-Carlos García-Pagán
Hepatic Hemodynamic Laboratory, Liver Unit, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
Dr. Juan-Carlos GARCIA-PAGÁN, Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain. Tel.: +34 93 227 54 00 ext. 3330 Fax: +34 93 227 93 48 E-mail: [email protected]Search for more papers by this authorAndrea De Gottardi
Hepatic Hemodynamic Laboratory, Liver Unit, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
Hepatology, Department of Clinical Research, University of Berne, Switzerland
The authors share the first authorship.
Search for more papers by this authorSusana Seijo
Hepatic Hemodynamic Laboratory, Liver Unit, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
The authors share the first authorship.
Search for more papers by this authorMontserrat Milá
Biochemical and Molecular Genetics Department, Hospital Clínic, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III, Spain
Search for more papers by this authorM. Isabel Alvarez
CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III, Spain
Search for more papers by this authorMiquel Bruguera
Hepatic Hemodynamic Laboratory, Liver Unit, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
Search for more papers by this authorJuan G. Abraldes
Hepatic Hemodynamic Laboratory, Liver Unit, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
Search for more papers by this authorJaime Bosch
Hepatic Hemodynamic Laboratory, Liver Unit, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
Search for more papers by this authorCorresponding Author
Juan-Carlos García-Pagán
Hepatic Hemodynamic Laboratory, Liver Unit, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
Dr. Juan-Carlos GARCIA-PAGÁN, Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain. Tel.: +34 93 227 54 00 ext. 3330 Fax: +34 93 227 93 48 E-mail: [email protected]Search for more papers by this authorAbstract
In idiopathic portal hypertension (IPH) typical vascular lesions are present in the branches of the portal vein or in the perisinusoidal area of the liver. Similar histological alterations have been reported in the pulmonary vasculature of patients with idiopathic pulmonary artery hypertension (IPAH). As IPAH is associated with mutations of the bone morphogenetic protein receptor 2 (BMPR2) gene, the aim of this study was to investigate whether this association might also be found in patients with IPH. Twenty-three samples belonging to 21 unrelated caucasian patients with IPH followed in the hepatic haemodynamic laboratory of the Hospital Clinic in Barcelona were included in the study. All patients were studied for the entire open reading frame and splice site of the BMPR2 gene by direct sequencing and multiple ligation probe amplification (MLPA) in order to detect large deletions/duplications. None of the 23 patients had pulmonary artery hypertension. Four patients presented one single nucleotide polymorphism (SNP) in intron 5, four patients had a SNP in exon 12 and a SNP in exon 1 was found in two cases. Two patients had both intron 5 and exon 12 polymorphisms. All SNPs were previously described. Except for these three SNPs, neither mutations nor rearrangements have been identified in the BMPR2 gene in this population. We did not detect mutations or rearrangements in the coding region of the BMPR2 gene in our patients with IPH. These findings suggest that, in contrast to IPAH, mutations in BMPR2 are not involved in the pathogenesis of IPH.
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