Genotype-phenotype Association in Hereditary Hemorrhagic Telangiectasia

Genotype-phenotype Association Study of ENG and ACVRL1 Genes in the Inflammatory and Endothelial Response in Hereditary Hemorrhagic Telangiectasia (HHT)

The present project aims to study the inflammatory and endothelial responses involved in the differences in clinical events related to both genotypes (ENG vs. ACVRL1) in HHT. Accordingly, a cross-sectional study is proposed to evaluate the differences in circulating inflammatory and endothelial biomarkers, including interleukines, adhesion molecules, chemokines and immune regulatory molecules between both HHT groups.

Background and rationale: Hereditary Hemorrhagic Telangiectasia (HHT) is a rare disease characterized by a multisystemic vascular dysplasia with autosomal dominant inheritance, mainly caused by mutations in ENG and ACVRL1 genes. Even though those mutations have been related to different clinical manifestations, the molecular mechanisms involved in each genetic variant have not been clarified. Methods: A cohort study will be carried out to compare the incidence of clinical events after a 12-months follow-up. The ability of these biomarkers to predict the clinical events will be assessed in a multivariate analysis.

Inclusion Criteria:

• Age between 18 and 75 years.
• Confirmed diagnosis of HHT, according to the Curaçao criteria or genetic diagnosis.
• Clinically stable condition at the time of inclusion, defined as score < 7 points on the Epistaxis Severity Score (ESS).
• Having signed the informed consent, after having received all the information concerning the study.

Exclusion Criteria:

• Major coronary or cerebrovascular event in the 3 months prior to inclusion.
• Serious intercurrent illnesses, such as acute infections, outbreaks of autoimmune or inflammatory pathology, active cancer, or other pathologies that, at the investigator's discretion, could interfere with the conduct of the study.
• Major surgery during the 2 months prior to inclusion.
• Pharmacological treatment maintained during the 3 months prior to inclusion with NSAIDs, corticosteroids or chemotherapy.
• Toxic habits, including severe smoking, alcohol or drug abuse, which in the opinion of the investigator could interfere with the conduct of the study.
• Pregnancy or puerperium.
• Any other condition that limits compliance with the visits or procedures established in the protocol.