Genomic Approaches to Dissect Human Host-pathogen Interactions in the Amazonian Rainforest

NCT05981378 | Not Yet Recruiting

• 1 other identifier: 210828
• Study Type: observational
• Target: 300
• Locations: 0 countries
• Sites: N/A

Brief Summary

This observational study, aims to characterize with a multi-omic approach, the impact of host genetics and the pathogenic environment on immune response variation in Native Amazonians in comparison with Mestizo Amazonian, a severely underrepresented population in genomic studies. Various samples will be taken from the participants, including blood, urine, saliva, etc. From the blood sample, peripheral blood mononuclear cells will be obtained and will give us information about the differences between immune response variation of Amazonian population. From the other samples we will be able to obtain additional information on the risk factors related to the difference in the immune response of the participants.

Conditions

Host-Pathogen Interactions

Keywords

Tropical Rainforest; Genomics

Outcome Measures

Primary Outcomes (4)

• Genes showing different transcriptional profiles and methylation pattern according environment, genetic ancestry and past viral exposure

  We will measure genome-wide expression profiles in peripheral blood mononuclear cells after stimulation for 6 hours with: (i) dengue virus, a major public health burden in the region, (ii) gardiquimod, an imidazoquinoxaline compound that activates toll like receptor 7/toll like receptor 8, able to sense viruses and intracellular pathogens; and (iii) lipopolysaccharide, a toll like receptor 4 agonist, to obtain a general view of responses to viruses and bacteria. Gene expression profiles will be measured using RNA-seq.

  Baseline

• Genetic and epigenetic diversity of amazonian population

  Using saliva from participants as source of DNA, we will perform whole-genome sequencing (WGS) at 8-10xcoverage.

  Baseline

• Impact of microbial exposures on immune response

  The viral exposome will be characterized in the 300 donors using a new tool call "VirScan", which identifies antibodies against \>600 pathogens and allergens, including viruses (\>1,200 viral strains) that are highly prevalent in the Amazonian, such as dengue, hepatitis B/C/D, or Mayaro virus.

  Baseline

• Genetic variants associated wit transcriptional response to immune activation and DNA methylation variation

  We will assess the host genetic factors controlling transcriptional responses and methylated DNA levels by mapping expression and methylation quantitative trait loci (eQTL and methylated eQTLs, respectively).

  Baseline

Secondary Outcomes (2)

• Demographic and admixture history of amazonian population

  Baseline

• Natural selection role in shaping immune response variation in Amazonians

  Baseline

Study Arms (2)

Native Amazonian group

Amazonian people that belongs to a indigenous community located in the Peruvian Amazon

Urban Amazonian mestizos group

Amazonian mestizo people that lives on a urban district in the Peruvian Amazon

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Amazonian Peruvian Native American and Amazonian mestizo population between 2023-2024

You may qualify if:

• People over 18 years of age who agree to participate in the study and sign the informed consent
• People whose parents and grandparents were born in the Peruvian Amazon.
• For volunteers from native communities, whose parents and grandparents belong to the same native community.

You may not qualify if:

• People who do not wish to have 40 mL of blood taken
• People who are passing through a febrile illness (fever during the last 5 days to the date of enrollment).
• Pregnant women
• People over 65 years old
• Breastfeeding women.

Sponsors & Collaborators

• Universidad Peruana Cayetano Heredia: lead
• Institut Pasteur: collaborator

Related Links

• Web page of the ethical review board of Universidad Peruana Cayetano Heredia

Biospecimen

Retention: SAMPLES WITH DNA

Whole Blood, serum, plasma, saliva, feces, peripheral blood mononuclear cells,

Central Study Contacts

Meddly Santoalla, PhD

CONTACT

+51 914068043; meddly.santolalla.r@upch.pe

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2023
• First Posted: August 8, 2023
• Study Start: August 2, 2024
• Primary Completion: November 20, 2024
• Study Completion: January 30, 2025
• Last Updated: April 24, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share