title: Polymorphisms at GLUT1 gene are not associated with the development of TSP/HAM in Brazilian HTLV-1 infected individuals and the discovery of a new polymorphism at GLUT1 gene.
abstract: The development of HTLV-1 associated clinical manifestations, such as TSP/HAM and ATLL, occur in 2-4% of the infected population and it is still unclear why this infection remains asymptomatic in most infected carriers. Recently, it has been demonstrated that HTLV uses the Glucose transporter type 1 (GLUT1) to infect T-CD4(+) lymphocytes and that single nucleotide polymorphisms (SNP) in the GLUT1 gene are associated with diabetic nephropathy in patients with diabetes mellitus in different populations. These polymorphisms could contribute to a higher GLUT1 protein expression on cellular membrane, facilitating the entry of HTLV and its transmission cell by cell. This could result in a higher provirus load and consequently in the development of TSP/HAM. To evaluate the role of GLUT1 gene polymorphisms in the development of TSP/HAM in HTLV-1 infected individuals, the g.22999G > T, g.15339T > C and c.-2841A > T sites were analyzed by PCR/RFLP or sequencing in 244 infected individuals and 102 normal controls. The proviral load of the HTLV-1 infected patients was also analyzed using Real Time Quantitative PCR. Genotypic and allelic frequencies of the three sites did not differ significantly between controls and HTLV-1 infected individuals. There was no difference in genotypic and allelic distributions among patients as to the presence or absence of HTLV-1 associated clinic manifestations. As regards the quantification of the provirus load, we observed a significant reduction in the asymptomatic individuals compared with the oligosymptomatic and TSP/HAM individuals. These results suggest that g.22999G > T, g.15339T > C, and c.-2841A > T SNP do not contribute to HTLV-1 infection nor to the genetic susceptibility of TSP/HAM in Brazilian HTLV-1 infected individuals.
authors.affiliation: Laboratório Avançado de Saúde Pública, Centro de Pesquisa Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.
authors.forename: Giselle Calasans Souza
authors.initials: GC
authors.lastname: Costa
authors.forename: Rochele
authors.initials: R
authors.lastname: Azevedo
authors.forename: Sandra Rocha
authors.initials: SR
authors.lastname: Gadelha
authors.forename: Simone Haddad
authors.initials: SH
authors.lastname: Kashima
authors.forename: Gabriel
authors.initials: G
authors.lastname: Muricy
authors.forename: Viviana Nila
authors.initials: VN
authors.lastname: Olavarria
authors.forename: Dimas Tadeu
authors.initials: DT
authors.lastname: Covas
authors.forename: Osvaldo Massaiti
authors.initials: OM
authors.lastname: Takayanagui
authors.forename: Bernardo
authors.initials: B
authors.lastname: Galvão-Castro
authors.forename: Luiz Carlos Júnior
authors.initials: LC
authors.lastname: Alcantara
mesh_terms: D001938:Brazil / Q000453:epidemiology; D005787:Gene Frequency; D005838:Genotype; D051272:Glucose Transporter Type 1 / Q000235:genetics*; D015490:HTLV-I Infections / Q000453:epidemiology / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D015493:Paraparesis, Tropical Spastic / Q000453:epidemiology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification
chemical_list: D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human