IL28B Gene Polymorphism SNP rs8099917 Genotype GG Is Associated with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in HTLV-1 Carriers

Background The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) are associated with HAM/TSP. Methods The study included 229 subjects, classified according to their neurological status in two groups: Group I (136 asymptomatic HTLV-1 carriers) and Group II (93 HAM/TSP patients). The proviral loads were quantified, and the rs8099917 and rs12979860 SNPs in the region of IL28B-gene were analyzed by StepOnePlus Real-time PCR System. Results A multivariate model analysis, including gender, age, and HTLV-1 DNA proviral load, showed that IL28B polymorphisms were independently associated with HAM/TSP outcome in rs12979860 genotype CT (OR = 2.03; IC95% = 0.96–4.27) and in rs8099917 genotype GG (OR = 7.61; IC95% = 1.82–31.72). Conclusion Subjects with SNP rs8099917 genotype GG and rs12979618 genotype CT may present a distinct immune response against HTLV-1 infection. So, it seems reasonable to suggest that a search for IL28B polymorphisms should be performed for all HTLV-1-infected subjects in order to monitor their risk for disease development; however, since this is the first description of such finding in the literature, we should first replicate this study with more HTLV-1-infected persons to strengthen the evidence already provided by our results.

[1]  E. Rondinelli,et al.  Interleukin 28B-related polymorphisms: a pathway for understanding hepatitis C virus infection? , 2013, World journal of gastroenterology.

[2]  E. Sabino,et al.  Lack of evidence to support the association of a single IL28B genotype SNP rs12979860 with the HTLV-1 clinical outcomes and proviral load , 2012, BMC Infectious Diseases.

[3]  A. Gessain,et al.  Epidemiological Aspects and World Distribution of HTLV-1 Infection , 2012, Front. Microbio..

[4]  V. Soriano,et al.  Development of tropical spastic paraparesis in human T-lymphotropic virus type 1 carriers is influenced by interleukin 28B gene polymorphisms. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[5]  H. Hoshino Cellular Factors Involved in HTLV-1 Entry and Pathogenicit , 2012, Front. Microbio..

[6]  Yasuaki Yamada,et al.  Paradoxical expression of IL-28B mRNA in peripheral blood in human T-cell leukemia virus Type-1 mono-infection and co-infection with hepatitis C Virus , 2012, Virology Journal.

[7]  J. Pinho,et al.  IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population , 2011, Liver international : official journal of the International Association for the Study of the Liver.

[8]  P. Ferenci,et al.  Early virologic response and IL28B polymorphisms in patients with chronic hepatitis C genotype 3 treated with peginterferon alfa-2a and ribavirin. , 2011, Journal of hepatology.

[9]  C. Thio,et al.  IL28B and the control of hepatitis C virus infection. , 2010, Gastroenterology.

[10]  J. Goedert,et al.  IL28B polymorphism does not determine outcomes of hepatitis B virus or HIV infection. , 2010, The Journal of infectious diseases.

[11]  Sven Bergmann,et al.  Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. , 2010, Gastroenterology.

[12]  C. Thio,et al.  Interleukin-28b: a key piece of the hepatitis C virus recovery puzzle. , 2010, Gastroenterology.

[13]  Limin Chen,et al.  ISG15, a ubiquitin-like interferon-stimulated gene, promotes hepatitis C virus production in vitro: implications for chronic infection and response to treatment. , 2010, The Journal of general virology.

[14]  A. Duarte,et al.  The Elevated Interferon Gamma Production is an Important Immunological Marker in HAM/TSP Pathogenesis , 2009, Scandinavian journal of immunology.

[15]  Thomas Berg,et al.  IL28B is associated with response to chronic hepatitis C interferon-α and ribavirin therapy , 2009, Nature Genetics.

[16]  Jacques Fellay,et al.  Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance , 2009, Nature.

[17]  Tom R. Gaunt,et al.  American Journal of Epidemiology Practice of Epidemiology Hardy-weinberg Equilibrium Testing of Biological Ascertainment for Mendelian Randomization Studies , 2022 .

[18]  A. Duarte,et al.  High production of RANTES and MIP-1α in the tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) , 2007, Journal of Neuroimmunology.

[19]  G. Gallagher,et al.  Human interferon lambda-1 (IFN-lambda1/IL-29) modulates the Th1/Th2 response. , 2007, Genes and immunity.

[20]  G. Gallagher,et al.  Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response , 2007, Genes and Immunity.

[21]  Inês Dourado,et al.  Perfil sociodemográfico, epidemiológico e comportamental de mulheres infectadas pelo HTLV-1 em Salvador-Bahia, uma área endêmica para o HTLV , 2007 .

[22]  I. Dourado,et al.  [Sociodemographic, epidemiological and behavioral profile of women infected with HTLV-1 in Salvador, Bahia, an endemic area for HTLV]. , 2007, Revista da Sociedade Brasileira de Medicina Tropical.

[23]  F. Proietti,et al.  Immunologic markers, uveitis, and keratoconjunctivitis sicca associated with human T-cell lymphotropic virus type 1. , 2006, American journal of ophthalmology.

[24]  P. Marchiori,et al.  Human T-cell lymphotropic virus type I (HTLV-I) proviral DNA viral load among asymptomatic patients and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis. , 2005, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[25]  A. Lézin,et al.  Quantitation of HTLV-I proviral load by a TaqMan real-time PCR assay. , 2002, Journal of virological methods.

[26]  A. Lloyd,et al.  The Influence of HLA Class I Alleles and Heterozygosity on the Outcome of Human T Cell Lymphotropic Virus Type I Infection1 , 2000, The Journal of Immunology.

[27]  R. Edlich,et al.  Global epidemic of human T-cell lymphotropic virus type-I (HTLV-I). , 2000, The Journal of emergency medicine.

[28]  J. Dipierri,et al.  Characteristic distribution of HTLV type I and HTLV type II carriers among native ethnic groups in South America. , 1999, AIDS research and human retroviruses.

[29]  S. Izumo,et al.  Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP. , 1999, Journal of neurovirology.

[30]  M. Levin,et al.  Immunopathogenesis of HTLV-I associated neurologic disease: massive latent HTLV-I infection in bone marrow of HAM/TSP patients. , 1997, Leukemia.

[31]  G. Burgess,et al.  Cyclic AMP negatively controls c-myc transcription and G1 cell cycle progression in p210 BCR-ABL transformed cells: inhibitory activity exerted through cyclin D1 and cdk4 , 1997, Leukemia.

[32]  H. Towler,et al.  Adult T-cell leukemia : antigen in an ATL cell line and detection of antibodies to the antigen in human sera , 2022 .