Journal of Medical Virology 80:2141–2146 (2008) 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 Sandra Rocha Gadelha, 1,2 Luiz Carlos Junior Alca ˆ ntara, 1,2 Gisele Calazans Costa, 1 Angelina Xavier Acosta, 1,3 Domingos Rios, 4 Simone Kashima, 5 Dimas Tadeu Covas, 5 and Bernardo Galva ˜ o-Castro 1,2 * 1 Laborato ´rio Avanc ¸ado de Sau ´ de Pu ´ blica/Centro de Pesquisas Gonc ¸alo Moniz/Fundac ¸a ´ o Oswaldo Cruz, Salvador, Bahia, Brazil 2 Escola Bahiana de Medicina e Sau ´ de Pu ´ blica/Fundac ¸a ˜ o para o Desenvolvimento das Cie ˆncias, Salvador, Bahia, Brazil 3 Departamento de Pediatria, Faculdade de Medicina, Universidade Federal da Bahia (UFBA), Bahia, Brazil 4 Laborato ´rio de Gene ´tica Molecular, Departamento de Cieˆncias Biolo ´gicas (DCB), Universidade Estadual do Sudoeste da Bahia (UESB), Bahia, Brazil 5 Hemocentrode Ribeira˜oPreto, Sa˜o Paulo, Brazil HTLV-1 is the etiologic agent of ATL and HAM/ TSP. The majority of HTLV-1-infected individuals remain asymptomatic, indicating that the infec- tion alone is not sufficient to cause the diseases. It has been reported that cytokine gene polymor- phisms, 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 poly- morphisms 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 ¼ 0.038) and asymp- tomatic (9.5%; P ¼ 0.025) subjects. Similarly, the 174G allele frequencies were higher in HAM/ TSP patients than in oligosymptomatic patients (P ¼ 0.02). Moreover, the 634GC/174GG geno- type combination was identified at a higher frequency (38.5%) in the HAM/TSP patients than in subjects with other clinical status (8.7%; P ¼ 0.016 for oligosymptomatic and 15.5%, P ¼ 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] ¼ 5.31; 95% [CI] ¼ 1.60–17.56; P ¼ 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. J. Med. Virol. 80:2141–2146, 2008. ß 2008 Wiley-Liss, Inc. KEY WORDS: HTLV-1; interleukin-6; interleukin- 10; polymorphisms; Brazilian populations INTRODUCTION The human T-cell lymphotropic virus type 1 (HTLV-1) (Family Retroviridae, subfamily Orthovirinae, genus Deltaretrovirus, species Primate T-lymphotropic virus I) is the etiologic agent of adult T-cell leukemia (ATL) and tropical spastic paraparesis/HTLV-1-associated mielopathy (HAM/TSP) [Poiesz et al., 1980; Gessain et al., 1985; Osame et al., 1986]. The majority of HTLV-1- infected individuals remain asymptomatic (95–98%), indicating that the infection alone is not sufficient to cause the diseases [Murphy et al., 1989; Orland et al., 2003]. It has been demonstrated that the Tax protein of HTLV is a transcriptional activator of viral and host cellular genes, including interleukin 2 (IL-2), the a chain of the IL-2 receptor (IL-2Ra), interleukin 6 (IL-6), interleukin 10 (IL-10), c-fos, granulocyte-macrophage *Correspondence to: Prof. Bernardo Galva ˜ o-Castro, MD, PhD, LASP/CPqGM/FIOCRUZ 121, rua Waldemar Falca ˜ o, Candeal 40296710 Salvador, BA, Brazil. E-mail: bgalvao@cpqgm.fiocruz.br Accepted 19 August 2008 DOI 10.1002/jmv.21341 Published online in Wiley InterScience (www.interscience.wiley.com) ß 2008 WILEY-LISS, INC.