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

Host-Pathogen Interactions Clinical Trial

— PATHO-NAT  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05981378
• Other study ID #: 210828
• Status: Not yet recruiting
• Start date: August 2, 2024
• Est. completion date: January 30, 2025

Study information

• Verified date: April 2024
• Source: Universidad Peruana Cayetano Heredia
• Contact: Meddly Santoalla, PhD
• Phone: +51 914068043
• Email: meddly.santolalla.r[@]upch.pe
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

The Amazon rainforest is characterized by adverse climatic conditions and a great diversity of pathogenic microorganisms that, consequently, would generate a selective pressure on the human immune response with a high impact on mortality. Some of the best characterized examples of human genetic adaptation have been related to infections; for example, the alleles causing sickle cell anemia, thalassemia and malaria. In addition, the introduction of infectious diseases from the "old world" during Spanish colonization in the 15th century and the urbanization of the last few centuries in the Amazon has also generated rapid adaptation that could drive variation in immune response. However, the evolutionary mechanisms that contributed to the adaptation of human defense against the aforementioned phenomena and events in this region are poorly understood. For this reason, studying these human genetic mechanisms in native populations would allow us to identify new genes that would be associated with resistance to infections, and also to explore the signs of rapid adaptation to the environment to which Amazonian populations have been exposed throughout their history.

We propose to study the variation of the immune system in Amazonian populations, studying together the degree of diversity with different approaches: genomic, epi-genomic and transcriptomic of the host and viral exposome, taking into consideration sociodemographic characteristics and comorbidities, which may shape the immune response. This study will provide new insights into variants in the human genome that affect the immune response, thereby increasing our understanding of the etiology and susceptibility to immune-related diseases, mainly tropical infectious diseases. Because human genetic studies are underrepresented in Native American populations, the knowledge gained would reduce the existing inequality in health knowledge between Native and non-Native populations.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: January 30, 2025
• Est. primary completion date: November 20, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Host-Pathogen Interactions

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Universidad Peruana Cayetano Heredia	Institut Pasteur

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	Demographic and admixture history of amazonian population	Using saliva from participants as source of DNA, we will perform whole-genome sequencing (WGS) at 8-10xcoverage.	Baseline
Secondary	Natural selection role in shaping immune response variation in Amazonians	We will employ an enrichment approach to test whether eQTLs, associated to specific cell-types or conditions, have been preferentially targeted by selection.	Baseline

External Links

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