NEW YORK – New research suggests that individuals from populations in parts of Africa where the malaria-causing parasite Plasmodium falciparum is prevalent tend to have shorter-than-usual telomeres tacked to the ends of chromosomes found in their white blood cells, or leukocytes.
"This association between malaria and [leukocyte telomere length (LTL)] appears larger than any other known exposure or behavior that has been investigated in large-scale studies," co-senior author Sarah Tishkoff, a geneticist and biologist at the University of Pennsylvania and director of UPenn's Center for Global Genomics and Health Equity, said in a statement.
For a study published in the American Journal of Human Genetics on Thursday, she and her colleagues from several international centers found that while genetic factors did affect LTL in populations from sub-Saharan Africa, telomere length also appeared to reflect exposure to P. falciparum, declining in regions where the malaria parasite is endemic.
Because telomere shortening has been implicated in everything from aging and age-related disease risk to predictions of mortality, the authors explained, the work sought to understand genetic and environmental factors affecting telomere length outside of European ancestry populations, where most past research has focused.
For their analyses, the researchers used terminal restriction fragmentation and Southern blotting experiments to profile LTL in relation to array-based genotypes, environmental factors, climate patterns, and more in 1,818 individuals from Tanzania, Botswana, Ethiopia, and Cameroon, including participants from ethnically diverse groups in areas with or without malaria endemicity.
Along with an overall increase in LTL in the sub-Saharan African individuals compared with European individuals profiled in the past, the team saw pronounced LTL variation across African populations, ranging from short LTLs in individuals from Fulani pastoralist groups from Cameroon to longer white blood cell telomeres in San hunter-gathers in Botswana.
Around half of the variation in telomere length was due to genetic contributors, the researchers reported. But their results also revealed a higher-than-anticipated effect for the presence of P. falciparum, potentially reflecting white blood cell responses to the known red blood cell, or erythrocyte, destruction that takes place during malaria infection.
"[W]e observe a significant negative association between Plasmodium falciparum malaria endemicity and LTL, while adjusting for age, sex, and genetics," the authors wrote, adding that "one potential mechanism may involve malaria-induced bouts of massive erythrocyte destruction and erythropoiesis, by which malaria may shorten LTL."
Moreover, investigators team speculated that the malaria impact on LTLs may stretch back into childhood, when individuals from malaria endemic areas typically experience repeated rounds of malaria infection, though they cautioned that the current study was not designed to test that hypothesis.
"Clearly, the next step in testing the relationship between malaria and LTL is to characterize LTL dynamics in children born and raised in regions of high malaria endemicity versus those born and raised in regions of low or no malaria endemicity," Tishkoff said.
The authors further noted that their results lined up with prior studies that pointed to significant LTL shortening in European ancestry individuals with acute malaria infection. Even so, they explained that "is it also possible that the geographic measure of malaria endemicity we use here is correlated with some unmeasured environmental, lifestyle, socio-economic, or pathogenic factor that may drive the association with LTL."