title: IL10A genotypic association with decreased IL-10 circulating levels in malaria infected individuals from endemic area of the Brazilian Amazon.
abstract: BACKGROUND
  Cytokines play an important role in human immune responses to malaria and variation in their production may influence the course of infection and determine the outcome of the disease. The differential production of cytokines has been linked to single nucleotide polymorphisms in gene promoter regions, signal sequences, and gene introns. Although some polymorphisms play significant roles in susceptibility to malaria, gene polymorphism studies in Brazil are scarce.
  
  
  METHODS
  A population of 267 individuals from Brazilian Amazon exposed to malaria was genotyped for five single nucleotide polymorphisms (SNPs), IFNG + 874 T/A, IL10A-1082G/A, IL10A-592A/C, IL10A-819 T/C and NOS2A-954G/C. Specific DNA fragments were amplified by polymerase chain reaction, allowing the detection of the polymorphism genotypes. The polymorphisms IL10A-592A/C and IL10A-819 T/C were estimated by a single analysis due to the complete linkage disequilibrium between the two SNPs with D' = 0.99. Plasma was used to measure the levels of IFN-γ and IL-10 cytokines by Luminex and nitrogen radicals by Griess reaction.
  
  
  RESULTS
  No differences were observed in genotype and allelic frequency of IFNG + 874 T/A and NOS2A-954G/C between positive and negative subjects for malaria infection. Interesting, the genotype NOS2A-954C/C was not identified in the study population. Significant differences were found in IL10A-592A/C and IL10A-819 T/C genotypes distribution, carriers of IL10A -592A/-819 T alleles (genotypes AA/TT + AC/TC) were more frequent among subjects with malaria than in negative subjects that presented a higher frequency of the variant C allele (p < 0.0001). The presence of the allele C was associated with low producer of IL-10 and low parasitaemia. In addition, the GTA haplotypes formed from combinations of investigated polymorphisms in IL10A were significantly associated with malaria (+) and the CCA haplotype with malaria (-) groups. The IL10A-1082G/A polymorphism showed high frequency of heterozygous AG genotype in the population, but it was not possible to infer any association of the polymorphism because their distribution was not in Hardy Weinberg equilibrium.
  
  
  CONCLUSIONS
  This study shows that the IL10A-592A/C and IL10A-819 T/C polymorphisms were associated with malaria and decreased IL-10 levels and low parasite density suggesting that this polymorphism influence IL-10 levels and may influence in the susceptibility to clinical malaria.
authors: Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz/Fiocruz, Av. Brasil 4365, Manguinhos, Rio de Janeiro, Brazil. virginia@ioc.fiocruz.br.
authors: Virginia A
authors: VA
authors: Pereira
authors: Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz/Fiocruz, Av. Brasil 4365, Manguinhos, Rio de Janeiro, Brazil. jucasaar@ioc.fiocruz.br.
authors: Juan C
authors: JC
authors: Sánchez-Arcila
authors: Laboratório de Imunodiagnóstico /Departamento de Ciências Biológicas, Escola Nacional de Saúde Pública/Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil. teva@ioc.fiocruz.br.
authors: Antonio
authors: A
authors: Teva
authors: Laboratório de Simulídeos e Oncocercose, Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, Brazil. daiana@ioc.fiocruz.br.
authors: Daiana S
authors: DS
authors: Perce-da-Silva
authors: Instituto de Infectologia Emilio Ribas, São Paulo, São Paulo, Brazil. marianapvasconcelos@hotmail.com.
authors: Mariana P A
authors: MP
authors: Vasconcelos
authors: Centro Interdepartamental de Biologia Experimental e Biotecnologia, Universidade Federal de Rondônia, Porto Velho, Rondônia, Brazil. cleoniml@yahoo.com.br.
authors: Cleoni A M
authors: CA
authors: Lima
authors: Laboratório de Quimioterapia/Fiocruz, Porto Velho, Rondônia, Brazil and Universidade Federal de Rondônia, Porto Velho, Rondônia, Brazil. cesarinovet@hotmail.com.
authors: Cesarino J L
authors: CJ
authors: Aprígio
authors: Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz/Fiocruz, Av. Brasil 4365, Manguinhos, Rio de Janeiro, Brazil. rodrigo.nunes@bio.fiocruz.br.
authors: Rodrigo N
authors: RN
authors: Rodrigues-da-Silva
authors: Laboratório de Imunologia e Imunogenética, Instituto de Pesquisa Clínica Evandro Chagas (IPEC)/Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil. davisantos007@bol.com.br.
authors: Davi O
authors: DO
authors: Santos
authors: Laboratório de Simulídeos e Oncocercose, Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, Brazil. banic@ioc.fiocruz.br.
authors: Dalma M
authors: DM
authors: Banic
authors: Laboratório de Imunologia e Imunogenética, Instituto de Pesquisa Clínica Evandro Chagas (IPEC)/Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil. gloria.bonecini@ipec.fiocruz.br.
authors: Maria G
authors: MG
authors: Bonecini-Almeida
authors: Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz/Fiocruz, Av. Brasil 4365, Manguinhos, Rio de Janeiro, Brazil. josue@ioc.fiocruz.br.
authors: Josué C
authors: JC
authors: Lima-Júnior
authors: Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz/Fiocruz, Av. Brasil 4365, Manguinhos, Rio de Janeiro, Brazil. lila@ioc.fiocruz.br.
authors: Joseli
authors: J
authors: Oliveira-Ferreira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001938:Brazil / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood / Q000235:genetics; D019353:Endemic Diseases; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000097:blood* / Q000235:genetics*; D015810:Linkage Disequilibrium; D008288:Malaria / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018512:Parasitemia / Q000453:epidemiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: D016207:Cytokines; C508609:IL10 protein, human; D016753:Interleukin-10
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