title: IL28B gene polymorphisms and Th1/Th2 cytokine levels might be associated with HTLV-associated arthropathy.
abstract: The present study is the first investigation of the association between single nucleotide polymorphisms (SNPs - rs8099917, rs12979860 and rs8103142) of the IL28B gene and the development of human T-lymphotropic virus (HTLV)-associated arthropathy (HAA). Individuals with HAA exhibited low interleukin (IL) 6 (p<0.05) and high IL-10 (p<0.05) levels compared with asymptomatic patients. TNF-α/CD4(+) T cell count, TNF-α/CD8(+) T cell count and IFN-γ/proviral load positively correlated in asymptomatic patients. The allelic and genotypic frequencies did not differ between patients with HAA and asymptomatic patients. Seven haplotypes were detected in the investigated population, with haplotype CCT (p<0.05) being the most frequent among the HTLV-infected individuals, while haplotype TTG (p<0.05) was detected in the group with HAA only. Compared with asymptomatic patients, individuals with HAA and genotype TT (rs8099917) exhibited larger numbers of CD8(+) T cells (p<0.05) and higher proviral load levels (p<0.05). Those patients with HAA and genotypes CC (rs12979860) and TT (rs8103142) exhibited high TNF-β (p<0.05) and IFN-γ (p<0.05) levels. Those patients with HAA and genotype CT/TT (rs12979860) exhibited high IL-10 levels (p<0.05). These results suggest that haplotypes CCT and TTG might be associated with susceptibility to HTLV infection and progression to HAA, respectively. Genotype TT (rs8099917) might be a risk factor for elevation of the proviral load and CD8(+) T cell count. In addition, genotypes CC (rs12979860) and TT (rs8103142) seem to be associated with increased TNF-β and IFN-γ levels.
authors.affiliation: Laboratory of Virology (Laboratório de Virologia), Institute of Biological Sciences (Instituto de Ciências Biológicas), Federal University of Pará (Universidade Federal do Pará), Guamá, 66075-110 Belém, Pará, Brazil.
authors.forename: Keyla Santos Guedes
authors.initials: KS
authors.lastname: de Sá
authors.affiliation: Laboratory of Virology (Laboratório de Virologia), Institute of Biological Sciences (Instituto de Ciências Biológicas), Federal University of Pará (Universidade Federal do Pará), Guamá, 66075-110 Belém, Pará, Brazil.
authors.forename: Bárbara Brasil
authors.initials: BB
authors.lastname: Santana
authors.affiliation: Laboratory of Virology (Laboratório de Virologia), Institute of Biological Sciences (Instituto de Ciências Biológicas), Federal University of Pará (Universidade Federal do Pará), Guamá, 66075-110 Belém, Pará, Brazil.
authors.forename: Tuane Carolina
authors.initials: TC
authors.lastname: de Souza Ferreira
authors.affiliation: Tropical Medicine Unit (Núcleo de Medicina Tropical), Federal University of Pará (Universidade Federal do Para), Umarizal, 66050-240 Belém, Pará, Brazil.
authors.forename: Rita Catarina Medeiros
authors.initials: RC
authors.lastname: Sousa
authors.affiliation: Tropical Medicine Unit (Núcleo de Medicina Tropical), Federal University of Pará (Universidade Federal do Para), Umarizal, 66050-240 Belém, Pará, Brazil.
authors.forename: Cezar Augusto Muniz
authors.initials: CA
authors.lastname: Caldas
authors.affiliation: Laboratory of Virology (Laboratório de Virologia), Institute of Biological Sciences (Instituto de Ciências Biológicas), Federal University of Pará (Universidade Federal do Pará), Guamá, 66075-110 Belém, Pará, Brazil.
authors.forename: Vânia Nakauth
authors.initials: VN
authors.lastname: Azevedo
authors.affiliation: Laboratory of Virology (Laboratório de Virologia), Institute of Biological Sciences (Instituto de Ciências Biológicas), Federal University of Pará (Universidade Federal do Pará), Guamá, 66075-110 Belém, Pará, Brazil.
authors.forename: Rosimar Neris Martins
authors.initials: RN
authors.lastname: Feitosa
authors.affiliation: Laboratory of Virology (Laboratório de Virologia), Institute of Biological Sciences (Instituto de Ciências Biológicas), Federal University of Pará (Universidade Federal do Pará), Guamá, 66075-110 Belém, Pará, Brazil.
authors.forename: Luiz Fernando Almeida
authors.initials: LF
authors.lastname: Machado
authors.affiliation: Laboratory of Virology (Laboratório de Virologia), Institute of Biological Sciences (Instituto de Ciências Biológicas), Federal University of Pará (Universidade Federal do Pará), Guamá, 66075-110 Belém, Pará, Brazil.
authors.forename: Marluísa
authors.initials: M
authors.lastname: de Oliveira Guimarães Ishak
authors.affiliation: Laboratory of Virology (Laboratório de Virologia), Institute of Biological Sciences (Instituto de Ciências Biológicas), Federal University of Pará (Universidade Federal do Pará), Guamá, 66075-110 Belém, Pará, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ishak
authors.affiliation: Laboratory of Virology (Laboratório de Virologia), Institute of Biological Sciences (Instituto de Ciências Biológicas), Federal University of Pará (Universidade Federal do Pará), Guamá, 66075-110 Belém, Pará, Brazil. Electronic address: vallinoto@ufpa.br.
authors.forename: Antonio Carlos Rosário
authors.initials: AC
authors.lastname: Vallinoto
mesh_terms: D000483:Alleles; D001170:Arthritis, Infectious / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D017977:Deltaretrovirus / Q000502:physiology*; D006800:Deltaretrovirus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D054884:Host-Pathogen Interactions; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007372:Interferons; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007378:Interleukins / Q000235:genetics*; D018655:Lymphocyte Count; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D016207:Cytokines; D007371:Interferon-gamma; D007372:Interferons; D016753:Interleukin-10; D015850:Interleukin-6; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: HTLV-associated arthropathy; IL-28B; rs12979860; rs8099917; rs8103142