title: TOLLIP gene variant is associated with Plasmodium vivax malaria in the Brazilian Amazon.
abstract: Toll-interacting protein is a negative regulator in the TLR signaling cascade, particularly by impeding the TLR2 and, TLR4 pathway. Recently, TOLLIP was shown to regulate human TLR signaling pathways. Two common TOLLIP polymorphisms (rs5743899 and rs3750920) were reported to be influencing IL-6, TNF and IL-10 expression. In this study, TOLLIP variants were investigated to their relation to Plasmodium vivax malaria in the Brazilian Amazon.
  
  
  
  This cohort study was performed in the municipalities of Careiro and, Manaus, in Western Brazilian Amazon. A total of 319 patients with P. vivax malaria and, 263 healthy controls with no previous history of malaria were included in the study. Genomic DNA was extracted from blood collected on filter paper, using the QIAamp®DNA Mini Kit, according to the manufacturer's suggested protocol. The rs5743899 and rs3750920 polymorphisms of the TOLLIP gene were typed by PCR-RFLP.
  
  
  
  Homozygous individuals for the rs3750920 T allele gene had twice the risk of developing malaria when compared to individuals homozygous for the C allele (OR 2.0 [95% CI 1.23-3.07]; p = 0.004). In the dominant model, carriers the C allele indicates protection to malaria, carriers of the C allele were compared to individuals with the T allele, and the difference is highly significant (OR 0.52 [95% CI 0.37-0.76]; p = 0.0006). The linkage disequilibrium between the two polymorphisms was weak (r2= 0.037; D' = 0.27).
  
  
  
  These findings suggest that genes involved in the TLRs-pathway may be involved in malaria susceptibility. The association of the TOLLIP rs3750920 T allele with susceptibility to malaria further provides evidence that genetic variations in immune response genes may predispose individuals to malaria.
authors.affiliation: Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25-Dom Pedro, Manaus, Amazonas, CEP:69040-000, Brazil.|Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas (UEA), Manaus, AM, Brazil.
authors.forename: Larissa W
authors.initials: LW
authors.lastname: Brasil
authors.affiliation: Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25-Dom Pedro, Manaus, Amazonas, CEP:69040-000, Brazil.
authors.forename: Laila R A
authors.initials: LR
authors.lastname: Barbosa
authors.affiliation: Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25-Dom Pedro, Manaus, Amazonas, CEP:69040-000, Brazil.|Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas (UEA), Manaus, AM, Brazil.
authors.forename: Felipe J
authors.initials: FJ
authors.lastname: de Araujo
authors.affiliation: Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25-Dom Pedro, Manaus, Amazonas, CEP:69040-000, Brazil.|Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas (UEA), Manaus, AM, Brazil.
authors.forename: Allyson G
authors.initials: AG
authors.lastname: da Costa
authors.affiliation: Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25-Dom Pedro, Manaus, Amazonas, CEP:69040-000, Brazil.
authors.forename: Luan D O
authors.initials: LD
authors.lastname: da Silva
authors.affiliation: Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25-Dom Pedro, Manaus, Amazonas, CEP:69040-000, Brazil.|Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas (UEA), Manaus, AM, Brazil.
authors.forename: Suzana K
authors.initials: SK
authors.lastname: Pinheiro
authors.affiliation: Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25-Dom Pedro, Manaus, Amazonas, CEP:69040-000, Brazil.|Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas (UEA), Manaus, AM, Brazil.
authors.forename: Anne C G
authors.initials: AC
authors.lastname: de Almeida
authors.affiliation: Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25-Dom Pedro, Manaus, Amazonas, CEP:69040-000, Brazil.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kuhn
authors.affiliation: Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas (UEA), Manaus, AM, Brazil.
authors.forename: Sheila
authors.initials: S
authors.lastname: Vitor-Silva
authors.affiliation: Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas (UEA), Manaus, AM, Brazil.
authors.forename: Gisely C
authors.initials: GC
authors.lastname: de Melo
authors.affiliation: Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25-Dom Pedro, Manaus, Amazonas, CEP:69040-000, Brazil.|Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas (UEA), Manaus, AM, Brazil.
authors.forename: Wuelton M
authors.initials: WM
authors.lastname: Monteiro
authors.affiliation: Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25-Dom Pedro, Manaus, Amazonas, CEP:69040-000, Brazil.|Instituto de Pesquisas Leônidas & Maria Deane, FIOCRUZ, Manaus, AM, Brazil.
authors.forename: Marcus V G
authors.initials: MV
authors.lastname: de Lacerda
authors.affiliation: Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25-Dom Pedro, Manaus, Amazonas, CEP:69040-000, Brazil. ramasawm@gmail.com.|Faculdade de Medicina, Universidade Nilton Lins, Manaus, AM, Brazil. ramasawm@gmail.com.|Programa de Pós-Graduação em Imunologia Básica e Aplicada Universidade Federal do Amazonas (UFAM), Manaus, AM, Brazil. ramasawm@gmail.com.
authors.forename: Rajendranath
authors.initials: R
authors.lastname: Ramasawmy
mesh_terms: D000328:Adult; D001938:Brazil; D015331:Cohort Studies; D004198:Disease Susceptibility / Q000469:parasitology; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D016780:Malaria, Vivax / Q000235:genetics* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D010966:Plasmodium vivax / Q000502:physiology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C410602:TOLLIP protein, human
keywords: Amazon; Malaria; Plasmodium vivax; TOLLIP gene