title: HLA-G 3'-untranslated region polymorphisms are associated with HTLV-1 infection, proviral load and HTLV-associated myelopathy/tropical spastic paraparesis development.
abstract: Most human T-lymphotropic virus type 1 (HTLV-1)-infected patients remain asymptomatic throughout life. The factors associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development have not been fully elucidated; immunological and genetic factors may be involved. The association of 14 bp INS/DEL HLA-G polymorphism with HTLV-1 infection susceptibility has been reported previously. Here, other polymorphic sites at the HLA-G 3'-UTR (14-bp D/I, +3003C/T, +3010C/G, +3027A/C, +3035C/T, +3142C/G, +3187A/G and +3196C/G) were evaluated in 37 HTLV-1-infected individuals exhibiting HAM/TSP, 45 HTLV-1 asymptomatic carriers (HAC) and 153 uninfected individuals, followed up at University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil. It was observed that: (i) 14bpDI genotype is a risk factor for HTLV-1 infection, while the 14bpDD and +3142CC genotypes were associated with protection against infection; (ii) the +3142C allele and the +3003CT and +3142CC genotypes were associated with susceptibility, while 14bpII and +3003TT genotypes were associated with protection against HAM/TSP development; and (iii) the 14bpII, +3010CC, +3142GG and +3187AA genotypes were associated with lower HTLV-1 proviral load compared to respective counterpart genotypes. Findings that HLA-G has a well-recognized immunomodulatory role and that the genetic variability at HLA-G 3'-UTR may post-transcriptionally modify HLA-G production indicate a differential genetic susceptibility to: (i) the development of HTLV-1 infection, (ii) the magnitude of HTLV-1 proviral load and (iii) HAM/TSP development.
authors.affiliation: Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo CEP: 14049-900, Brazil.
authors.forename: Daiani Cristina
authors.initials: DC
authors.lastname: Cilião Alves
authors.affiliation: Faculdade de Ceilândia, Universidade de Brasília (UnB), Brasília, Distrito Federal CEP: 72220-900, Brazil.|Núcleo de Medicina Tropical, Universidade de Brasília (UnB), Brasília, Distrito Federal CEP: 70904-970, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Haddad
authors.affiliation: Fundação Hemocentro de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo CEP: 14051-140, Brazil.|Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo CEP: 14040-903, Brazil.
authors.forename: Maurício Cristiano
authors.initials: MC
authors.lastname: Rocha-Júnior
authors.affiliation: Fundação Hemocentro de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo CEP: 14051-140, Brazil.
authors.forename: Virgínia Mara
authors.initials: VM
authors.lastname: de Deus Wagatsuma
authors.affiliation: Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo CEP: 14049-900, Brazil.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Martelli-Palomino
authors.affiliation: Fundação Hemocentro de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo CEP: 14051-140, Brazil.
authors.forename: Adriana Aparecida
authors.initials: AA
authors.lastname: Marques
authors.affiliation: Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo CEP: 14049-900, Brazil.
authors.forename: Osvaldo Massaiti
authors.initials: OM
authors.lastname: Takayanagui
authors.affiliation: Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo CEP: 14049-900, Brazil.|Fundação Hemocentro de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo CEP: 14051-140, Brazil.
authors.forename: Dimas Tadeu
authors.initials: DT
authors.lastname: Covas
authors.affiliation: Fundação Hemocentro de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo CEP: 14051-140, Brazil.|Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo CEP: 14040-903, Brazil.
authors.forename: Simone
authors.initials: S
authors.lastname: Kashima
authors.affiliation: Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo CEP: 14049-900, Brazil.
authors.forename: Eduardo Antônio
authors.initials: EA
authors.lastname: Donadi
mesh_terms: D020413:3' Untranslated Regions; D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D059951:HLA-G Antigens / Q000235:genetics* / Q000276:immunology; D015490:HTLV-I Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000235:genetics* / Q000276:immunology / Q000821:virology; D011110:Polymorphism, Genetic; D011533:Proviruses / Q000235:genetics / Q000502:physiology*; D013118:Spinal Cord Diseases / Q000235:genetics* / Q000276:immunology / Q000821:virology; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D059951:HLA-G Antigens