Browsing by Autor "Carolinne de Sales Marques"

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    Meta-Analysis of Human Toll-Like Receptor-1 Polymorphisms rs4833095 and rs5743618 and Leprosy Development
    (2024) Luana Karen Correia dos Santos; Susana Oliveira P; Everly dos Menezes S; Bárbara dos Santos R C; Lucia Alvarado-Arnez E; Carolinne de Sales Marques
    Leprosy is a chronic infectious disease, with genetics fundamentally responsible for its outcome. Single nucleotide polymorphisms (SNPs) in immune response genes have been shown to participate in the disease. Human Toll-like receptor 1 (TLR1) in leprosy infection recognizes cell wall components and activates immunological responses, polymorphisms in TLR1 genes may control disease progression. Studies investigating SNPs in TLR1 have not reached a consensus. We performed a meta-analysis to evaluate the participation of TLR1 SNPs in leprosy infection. For that purpose, we searched online databases PubMed, LILACS, Scopus, and ScienceDirect for original articles investigating TLR1 polymorphisms and leprosy. Of 382 studies found, eight were included, and only two SNPs had sufficient studies to carry out the analysis: rs4833095 and rs5743618. No association was found for either of the SNPs evaluated. Only rs4833095 had enough studies to perform a subgroup analysis which also did not reach statistical significance. In conclusion, we demonstrated that the SNPs rs4833095 and rs5743618 were not associated with leprosy in this meta-analysis. We address the need for more studies with both SNPs once TLR1 is an essential receptor in M. leprae infection.
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    Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populations
    (Public Library of Science, 2021) Ohanna Cavalcanti de Lima Bezerra; Lucia Elena Alvarado-Arnez; Nédio Mabunda; Graça Salomé; Amina de Sousa; Fernanda S. G. Kehdy; Carolinne de Sales Marques; Fernanda Saloum de Neves Manta; Rafaela Mota Andrade; Laís Pereira Ferreira
    Pyruvate kinase (PK), encoded by the PKLR gene, is a key player in glycolysis controlling the integrity of erythrocytes. Due to Plasmodium selection, mutations for PK deficiency, which leads to hemolytic anemia, are associated with resistance to malaria in sub-Saharan Africa and with susceptibility to intracellular pathogens in experimental models. In this case-control study, we enrolled 4,555 individuals and investigated whether PKLR single nucleotide polymorphisms (SNPs) putatively selected for malaria resistance are associated with susceptibility to leprosy across Brazil (Manaus-North; Salvador-Northeast; Rondonópolis-Midwest and Rio de Janeiro-Southeast) and with tuberculosis in Mozambique. Haplotype T/G/G (rs1052176/rs4971072/rs11264359) was associated with leprosy susceptibility in Rio de Janeiro (OR = 2.46, p = 0.00001) and Salvador (OR = 1.57, p = 0.04), and with tuberculosis in Mozambique (OR = 1.52, p = 0.07). This haplotype downregulates PKLR expression in nerve and skin, accordingly to GTEx, and might subtly modulate ferritin and haptoglobin levels in serum. Furthermore, we observed genetic signatures of positive selection in the HCN3 gene (xpEHH>2 -recent selection) in Europe but not in Africa, involving 6 SNPs which are PKLR/HCN3 eQTLs. However, this evidence was not corroborated by the other tests (FST, Tajima's D and iHS). Altogether, we provide evidence that a common PKLR locus in Africans contribute to mycobacterial susceptibility in African descent populations and also highlight, for first, PKLR as a susceptibility gene for leprosy and TB.