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.
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.
Gadelha
Sandra Rocha
SR
Laboratório Avançado de Saúde Pública, Centro de Pesquisas Gonçalo Moniz/Fundaçáo Oswaldo Cruz, Salvador, Bahia, Brazil.
Junior Alcântara
Luiz Carlos
LC
Costa
Gisele Calazans
GC
Acosta
Angelina Xavier
AX
Rios
Domingos
D
Kashima
Simone
S
Covas
Dimas Tadeu
DT
Galvão-Castro
Bernardo
B
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
D015850:Interleukin-6; D016753:Interleukin-10