Genomic markers related to an increased propensity of High Altitude Cerebral and Pulmonary Edema (HACE and HAPE)

• Grant number: 20/12379-8
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2022
• End date: November 30, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Julio Flávio Meirelles Marchini
• Grantee: Julio Flávio Meirelles Marchini
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Denise Frediani Barbeiro ; Flavia Regina Rotea Mangone ; Heraldo Possolo de Souza ; Maria Aparecida Nagai ; Rodrigo Antonio Brandão Neto

Abstract

Acute Mountain Sickness (AMS), High Altitude Cerebral Edema (HACE), and High Altitude Pulmonary Edema (HAPE) are some of the diseases that can affect individuals living in low altitudes moving to high altitudes. To date, little is known about the genomic, epigenetic, and transcriptional changes that occur with acute exposure to altitude. Knowing these changes can help in understanding the pathophysiological mechanisms of altitude-related acute diseases and in the identification of susceptible individuals. HYPOTHESES: The transcriptional and epigenetic profile may be related to the development of acute diseases related to altitude. Individuals who live at low altitudes and had AMS, HACE and HAPE on high altitude short-term journeys may have particular genomic profiles that render them susceptible to acute altitude illnesses. METHOD: Brazilian members of high mountain expeditions to Argentina will be invited to participate in the study. The participants of the study will be submitted to peripheral blood collections in two moments: in basal conditions (in the city of São Paulo), and during exposure to hypoxia (from 2500m above sea level). Participants will be assessed for the development of MAA. We will assess whether there is a change between the transcription and methylation profile between blood samples according to the development of MAA. Blood samples will be analyzed according to altitude and symptom development to check if there was (1) alteration of the transcript profile of pre-defined transcribed genes and (2) genomic profile of methylation. At the same time, individuals who live in low altitudes and had AMS, HAPE and HACE on previous trips to high altitudes will be invited to participate in the complementary study that will map the genome to identify association with genes changes and single nucleotide polymorphisms. (AU)