Brazil, August 18, 2023 (ATB Digital). The conclusion was made based on the analysis of the genome of 118 people living in 19 cities of the region. The results, published in the journal Science Advances, could help guide the search for new treatments.
Yanomami indigenous people, Roraima, Brazil. The study analyzed 600,000 markers from the genome
The low incidence of Chagas disease (also called sleeping sickness) among the indigenous peoples of the Amazon may have a genetic explanation. In particular, a new study published in March in the scientific journal Science Advances points to a genetic variant present in the vast majority of people analyzed in the region that plays an important role in the parasite’s resistance to the infection it transmits. .
To reach this conclusion, 600,000 markers from the genomes of 118 individuals from 19 indigenous Amazonian jungle populations were analyzed. Researchers affiliated with the University of São Paulo (USP) in Brazil have found differences in genes involved in metabolism, the immune system, and resistance to infection by parasites such as Trypanosoma cruzi, which cause Chagas disease. One of the most common variants, present in a gene known by the acronym PPP3CA, occurs in 80% of the natives analyzed.
“The American continent was the last to be inhabited by modern humans and presents a great variety of environments. Without a doubt, this caused selective pressure on these people and caused an adaptation similar to what we are seeing now,” explained Kelly Nunez, a researcher at the USP Institute of Biological Sciences and one of the lead authors of the study, in a statement released to the Fapesp press agency.
According to the publication, the PPP3CA variant is also present in other populations, but with a lower frequency: 10% in Europe and 59% in Africa. The authors believe that this is no coincidence, since the African continent has areas with ecological conditions similar to those of the Amazon, and is home to another species of the parasite Trypanosoma brucei, which causes sleeping sickness. Evidence supports the role of the genetic variant as a protector against protozoal infections.
What is the relationship between genetics and resistance to Chagas disease?
To understand the role of the PPP3CA gene in interactions with the protozoa that cause Chagas disease, the group converted pluripotent stem cells (which can transform into any other human cell) into heart cells, which were divided into two control groups. In one part, PPP3CA gene expression was reduced by about 65% to mimic the genetic variation found in native populations. While the other kept the normal expression.
In cells with reduced gene expression, the infectivity of protozoa was approximately 25% lower than in cells with normal PPP3CA expression. This demonstrates that the gene, in its most common state in humans, promotes protozoan replication. This factor likely meant that native Amazonian ancestors who had the protective variant were less infected and survived the disease longer, passing the trait on to their descendants,” Nunes said in a statement to Fapesp.
One of the hypotheses put forward by the authors is that in addition to reducing the likelihood of infection, the genetic variant found in the study may also contribute to a milder form of the disease. In the general population, approximately 30% of people with Chagas disease develop a chronic form of the disease that causes heart failure and can be fatal.
“This does not mean that the indigenous people of the Amazon will never get Chagas disease, but those infected may be less likely to develop its chronic and even fatal phase,” Nunez explains.
According to the study, the emergence of a protective variant against Chagas disease may have occurred around 7,500 years ago, after Amazon populations split from Andean populations.
Source: National Geographic.
– ATB Digital