title: Correlation between polymorphisms at interleukin-6 but not at interleukin-10 promoter and the risk of human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis in Brazilian individuals.
abstract: HTLV-1 is the etiologic agent of ATL and HAM/TSP. The majority of HTLV-1-infected individuals remain asymptomatic, indicating that the infection alone is not sufficient to cause the diseases. It has been reported that cytokine gene polymorphisms, including polymorphisms at IL-6 and IL-10 gene, might be important. We analyzed SNP in the promoter region of the IL-6: -174, -572, -597, and -634 positions, and IL-10: -592 position to evaluate the role of these polymorphisms in the HAM/TSP pathogenesis in 133 HTLV-1 infected individuals and in 100 healthy individuals from Salvador, Bahia, Brazil. The -634C allele frequencies were higher among HAM/TSP patients (21.2%) than among oligosymptomatic (6.5%; P = 0.038) and asymptomatic (9.5%; P = 0.025) subjects. Similarly, the -174G allele frequencies were higher in HAM/TSP patients than in oligosymptomatic patients (P = 0.02). Moreover, the -634GC/-174GG genotype combination was identified at a higher frequency (38.5%) in the HAM/TSP patients than in subjects with other clinical status (8.7%; P = 0.016 for oligosymptomatic and 15.5%, P = 0.012 for asymptomatic patients). However, the multivariate logistic regression including the genotypes of the three studied loci showed that only -634 C IL-6 carriers remain as significant and independent TSP/HAM predictor (odds ratio [OR] = 5.31; 95% [CI] = 1.60-17.56; P = 0.006). We suggest that -634 G C in IL-6 could contribute to HAM/TSP development and that identification of the collective influence of several cytokine polymorphisms, their prevalence, and their interaction could help to better understand this disease.
authors.affiliation: Laboratório Avançado de Saúde Pública, Centro de Pesquisas Gonçalo Moniz/Fundaçáo Oswaldo Cruz, Salvador, Bahia, Brazil.
authors.forename: Sandra Rocha
authors.initials: SR
authors.lastname: Gadelha
authors.forename: Luiz Carlos
authors.initials: LC
authors.lastname: Junior Alcântara
authors.forename: Gisele Calazans
authors.initials: GC
authors.lastname: Costa
authors.forename: Angelina Xavier
authors.initials: AX
authors.lastname: Acosta
authors.forename: Domingos
authors.initials: D
authors.lastname: Rios
authors.forename: Simone
authors.initials: S
authors.lastname: Kashima
authors.forename: Dimas Tadeu
authors.initials: DT
authors.lastname: Covas
authors.forename: Bernardo
authors.initials: B
authors.lastname: Galvão-Castro
mesh_terms: D001938:Brazil / Q000453:epidemiology; D005787:Gene Frequency; D015490:HTLV-I Infections / Q000150:complications*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D016015:Logistic Models; D015999:Multivariate Analysis; D015493:Paraparesis, Tropical Spastic / Q000453:epidemiology* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D013118:Spinal Cord Diseases / Q000453:epidemiology* / Q000276:immunology
chemical_list: D015850:Interleukin-6; D016753:Interleukin-10