Influence of polymorphisms in toll-like receptors (TLRs) on malaria susceptibility in low-endemic area of the Atlantic Forest, Sao Paulo, Brazil
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Citações na Scopus
7
Tipo de produção
article
Data de publicação
2018
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER SCIENCE BV
Autores
FERNANDES, Francisco
CURADO, Izilda
HOLCMAN, Marcia M.
WUNDERLICH, Gerhard
SANTOS, Sidney E.
SOLER, Julia M.
Citação
ACTA TROPICA, v.182, p.309-316, 2018
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.
Palavras-chave
Malaria, Toll-like receptors, Genetic polymorphism, Association study, Logistic regression model, Principal components, Population structure correction
Referências
- Apinjohr TO, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0081071
- Arruda ME, 2007, MEM I OSWALDO CRUZ, V102, P367, DOI 10.1590/S0074-02762007005000041
- Bali P, 2013, HUM IMMUNOL, V74, P223, DOI 10.1016/j.humimm.2012.11.006
- Barreiro LB, 2009, PLOS GENET, V5, DOI 10.1371/journal.pgen.1000562
- Basu M, 2010, INFECT GENET EVOL, V10, P686, DOI 10.1016/j.meegid.2010.03.008
- Campino S, 2009, MALARIA J, V8, DOI 10.1186/1475-2875-8-44
- Costa AG, 2017, PLOS ONE, V12, DOI 10.1371/journal.pone.0183840
- Crisan TO, 2012, GENE, V494, P109, DOI 10.1016/j.gene.2011.12.008
- CVE (Centro de Vigilancia Epidemioldgica), 2008, B EPIDEMIOL PAUL, V5, P24
- Francez PAD, 2012, FORENSIC SCI INT-GEN, V6, P132, DOI 10.1016/j.fsigen.2011.04.002
- De Moura RR, 2015, AM J HUM BIOL, V27, P674, DOI 10.1002/ajhb.22714
- Manta FSD, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0075145
- de Oliveira CI, 1999, VACCINE, V17, P2959, DOI 10.1016/S0264-410X(99)00176-0
- dos Santos LC, 2009, VET PARASITOL, V163, P148, DOI 10.1016/j.vetpar.2009.03.042
- Esposito S, 2012, MALARIA J, V11, DOI 10.1186/1475-2875-11-196
- Fortin A, 2002, HUM MOL GENET, V11, P2469, DOI 10.1093/hmg/11.20.2469
- Greene JA, 2012, MALARIA J, V11, DOI 10.1186/1475-2875-11-47
- Greene JA, 2009, MALARIA J, V8, DOI 10.1186/1475-2875-8-50
- Guimaraes LO, 2018, HUM IMMUNOL, V79, P101, DOI [10.1015/j.humimm.2017.11.007, 10.1016/j.humimm.2017.11.007]
- Heinze G, 2006, STAT MED, V25, P4216, DOI 10.1002/sim.2687
- Hosmer D.W., 2000, APPL LOGISTIC REGRES
- Johnson R. A., 2002, APPL MULTIVARIATE ST
- Kar A, 2015, INFECT GENET EVOL, V36, P356, DOI 10.1016/j.meegid.2015.10.008
- Kirchgatter K, 2014, REV INST MED TROP SP, V56, P403, DOI 10.1590/S0036-46652014000500006
- Kleinbaum D.G, 1994, LOGISTIC REGRESSION
- Kwiatkowski D, 2000, CURR OPIN GENET DEV, V10, P320, DOI 10.1016/S0959-437X(00)00087-3
- Laayouni H, 2014, P NATL ACAD SCI USA, V111, P2668, DOI 10.1073/pnas.1317723111
- Ladeia-Andrade S, 2007, MEM I OSWALDO CRUZ, V102, P943, DOI 10.1590/S0074-02762007000800009
- Laird N.M., 2011, FUNDAMENTALS MODEM S
- Leoratti FMS, 2008, J INFECT DIS, V198, P772, DOI 10.1086/590440
- Lins TC, 2010, AM J HUM BIOL, V22, P187, DOI 10.1002/ajhb.20976
- Mockenhaupt FP, 2006, P NATL ACAD SCI USA, V103, P177, DOI 10.1073/pnas.0506803102
- Mockenhaupt FP, 2006, J INFECT DIS, V194, P184, DOI 10.1086/505152
- Mogensen TH, 2009, CLIN MICROBIOL REV, V22, P240, DOI 10.1128/CMR.00046-08
- Netea MG, 2012, NAT IMMUNOL, V13, P535, DOI 10.1038/ni.2284
- Oliveira-Ferreira J, 2010, MALARIA J, V9, DOI 10.1186/1475-2875-9-115
- Omar AH, 2012, MALARIA J, V11, DOI 10.1186/1475-2875-11-168
- Panigrahi S, 2016, IMMUNOL RES, V64, P291, DOI 10.1007/s12026-015-8749-7
- Paradowska E, 2016, PLOS ONE, V11, DOI 10.1371/journal.pone.0154100
- Pirahmadi S, 2013, CELL J, V15, P182
- PNUD (Programa das Nacoes Unidas pare o Desenvolvimento), 2013, ATL DES HUM BRAS 201
- Price AL, 2006, NAT GENET, V38, P904, DOI 10.1038/ng1847
- Quach H, 2016, CELL, V167, P643, DOI 10.1016/j.cell.2016.09.024
- R Development Core Team, 2010, R LANG ENV STAT COMP
- Sam-Agudu NA, 2010, AM J TROP MED HYG, V82, P548, DOI 10.4269/ajtmh.2010.09-0467
- Santos NPC, 2010, HUM MUTAT, V31, P184, DOI 10.1002/humu.21159
- Santos SD, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0036692
- Sawian CE, 2013, INNATE IMMUN-LONDON, V19, P174, DOI 10.1177/1753425912455675
- Soares SC, 2008, GENET MOL RES, V7, P1011, DOI 10.4238/vol7-4gmr439
- Tiwari HK, 2008, HUM HERED, V66, P67, DOI 10.1159/000119107
- Yim JJ, 2004, FEMS IMMUNOL MED MIC, V40, P163, DOI 10.1016/S0928-8244(03)00342-0
- Zakeri S, 2011, MALARIA J, V10, DOI 10.1186/1475-2875-10-77