Influence of polymorphisms in toll-like receptors (TLRs) on malaria susceptibility in low-endemic area of the Atlantic Forest, Sao Paulo, Brazil

Autor(es)

Guimaraes, Lilian O. ^[1] ; Fernandes, Francisco ^[2] ; Monteiro, Eliana F. ^[1] ; Curado, Izilda ^[3] ; Holcman, Marcia M. ^[4] ; Wunderlich, Gerhard ^[5] ; Santos, Sidney E. ^[6] ; Soler, Julia M. ^[2] ; Kirchgatter, Karin ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Trop Med, Superintendence Endem Dis Control, Malaria Res Ctr, BR-05403000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Math & Stat, Dept Stat, BR-05508090 Sao Paulo - Brazil

^[3] Superintendence Endem Dis Control, Lab Immunoepidemiol, BR-01027000 Sao Paulo - Brazil

^[4] Superintendence Endem Dis Control, Div Vector Control, BR-01027000 Sao Paulo - Brazil

^[5] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, BR-05508000 Sao Paulo - Brazil

^[6] Fed Univ Para, Inst Biol Sci, Lab Human & Med Genet, BR-66075110 Belem, Para - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Acta Tropica; v. 182, p. 309-316, JUN 2018.
• Citações Web of Science: 2

Resumo

In low-endemic areas for malaria transmission, asymptomatic individuals play an important role as reservoirs for malarial infection. Understanding the dynamics of asymptomatic malaria is crucial for its efficient control in these regions. Genetic host factors such as Toll-like receptor CUR) polymorphisms may play a role in the maintenance or elimination of infection. In this study, the effect of TLR polymorphisms on the susceptibility to malaria was investigated among individuals living in the Atlantic Forest of Sao Paulo, Southern Brazil. A hundred and ninety-five Brazilian individuals were enrolled and actively followed up for malaria for three years. Twenty-four polymorphisms in five toll-like receptor (TLR) genes were genotyped by RFLP, direct sequencing or fragment analysis. The genotypes were analyzed for the risk of malaria. Ongoing Plasmodium vivax or P. malaria infection, was identified by the positive results in PCR tests and previous P. vtvax malaria, was assumed when antiplasmodial antibodies against PvMSP1(19) were detected by ELISA. An evaluation of genomic ancestry was conducted using biallelic ancestry informative markers and the results were used as correction in the statistical analysis. Nine SNPs and one microsatellite were found polymorphic and three variant alleles in TLR genes were associated to malaria susceptibility. The regression coefficient estimated for SNP TLR9.-1237.T/C indicated that the presence of at least one allele C increased, on average, 2.3 times the malaria odds, compared to individuals with no allele C in this SNP. However, for individuals with the same sex, age and household, the presence of at least one allele C in SNP TLR9.-1486.T/C reduced, on average, 1.9 times the malaria odds, compared to individuals with no allele C. Moreover, this allele C plus an S allele in TLR6.P249S in individuals with same sex, age and ancestry, reduced, on average, 4.4 times the malaria odds. Our findings indicate a significant association of TLR9.-1237.T/C gene polymorphism with malarial infection and contribute to a better knowledge of the role of TLRs in malaria susceptibility in an epidemiological setting different from other settings. (AU)

• Processo FAPESP: 11/50492-1 - Estudo de polimorfismos geneticos em genes relacionados com a imunidade inata em populacao de area de baixa endemicidade para malaria.
• Beneficiário: Karin Kirchgatter Hildebrand
• Modalidade de apoio: Auxílio à Pesquisa - Regular