Association of apoptosis-related variants to malaria infection and parasite density in individuals from the Brazilian Amazon

• Published in: Malaria Journal
• Main Authors: Camille Sena-dos-Santos, Giovanna C. Cavalcante, Diego Marques, Caio S. Silva, Milene Raiol de Moraes, Pablo Pinto, Mayara Natália Santana-da-Silva, Rafaella S. Ferraz, Sheyla Patrícia T. Costa, Ana Maria R. Ventura, Marinete M. Póvoa, Maristela G. Cunha, Ândrea Ribeiro-dos-Santos
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2023
• Subjects: Malaria; Plasmodium; Apoptosis; Genetic ancestry; Genetic markers; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic; Indel’
• Online Access: https://doi.org/10.1186/s12936-023-04729-6; https://doaj.org/article/77a04ea34aa64aa087b00ffe0ff3c610

Abstract Background In malaria infection, apoptosis acts as an important immunomodulatory mechanism that leads to the elimination of parasitized cells, thus reducing the parasite density and controlling immune cell populations. Here, it was investigated the association of INDEL variants in apoptotic genes—rs10562972 (FAS), rs4197 (FADD), rs3834129 and rs59308963 (CASP8), rs61079693 (CASP9), rs4647655 (CASP3), rs11269260 (BCL-2), and rs17880560 (TP53)—and the influence of genetic ancestry with susceptibility to malaria and parasite density in an admixed population from the Brazilian Amazon. Methods Total DNA was extracted from 126 malaria patients and 101 uninfected individuals for investigation of genetic ancestries and genotypic distribution of apoptosis-related variants by Multiplex PCR. Association analyses consisted of multivariate logistic regressions, considering the following comparisons: (i) DEL/DEL genotype vs. INS/DEL + INS/INS; and (ii) INS/INS vs. INS/DEL + DEL/DEL. Results Individuals infected by Plasmodium falciparum had significantly higher African ancestry proportions in comparison to uninfected controls, Plasmodium vivax, and mixed infections. The INS/INS genotype of rs3834129 (CASP8) seemed to increase the risk for P. falciparum infection (P = 0.038; OR = 1.867; 95% CI 0.736–3.725), while the DEL/DEL genotype presented a significant protective effect against infection by P. falciparum (P = 0.049; OR = 0.446; 95% CI 0.185–0.944) and mixed infection (P = 0.026; OR = 0.545; 95% CI 0.281–0.996), and was associated with lower parasite density in P. falciparum malaria (P = 0.009; OR = 0.383; 95% CI 0.113–1.295). Additionally, the INS/INS genotype of rs10562972 (FAS) was more frequent among individuals infected with P. vivax compared to P. falciparum (P = 0.036; OR = 2.493; 95% CI 1.104–4.551), and the DEL/DEL genotype of rs17880560 (TP53) was significantly more present in patients with mono-infection by P. vivax than in individuals with mixed infection (P = 0.029; OR = 0.667; 95% CI 0.211–1.669). ...