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

Autor: Sena-Dos-Santos C; Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA), Belém, Brazil., Cavalcante GC; Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA), Belém, Brazil., Marques D; Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA), Belém, Brazil., Silva CS; Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA), Belém, Brazil., de Moraes MR; Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA), Belém, Brazil., Pinto P; Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA), Belém, Brazil.; Laboratory of Dermatoimmunology, Federal University of Pará (UFPA), Marituba, Brazil., Santana-da-Silva MN; Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA), Belém, Brazil., Ferraz RS; Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA), Belém, Brazil., Costa SPT; Laboratory of Microbiology and Immunology, Federal University of Pará (UFPA), Belém, Brazil., Ventura AMR; Division of Parasitology, Evandro Chagas Institute (IEC), Ananindeua, Brazil., Póvoa MM; Division of Parasitology, Evandro Chagas Institute (IEC), Ananindeua, Brazil., Cunha MG; Laboratory of Microbiology and Immunology, Federal University of Pará (UFPA), Belém, Brazil., Ribeiro-Dos-Santos Â; Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA), Belém, Brazil. akelyufpa@gmail.com.; Program of Oncology and Medical Sciences, Oncology Research Center, Belém, Brazil. akelyufpa@gmail.com.
Jazyk: angličtina
Zdroj: Malaria journal [Malar J] 2023 Oct 04; Vol. 22 (1), pp. 295. Date of Electronic Publication: 2023 Oct 04.
DOI: 10.1186/s12936-023-04729-6
Abstrakt: 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).
Conclusions: In conclusion, variants in apoptosis genes are associated with malaria susceptibility and parasite density, indicating the role of apoptosis-related genetic profiles in immune responses against malaria infection.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje