Leprosy is an immunopathology caused by M. leprae ; its evolution depends on immunological and genetic aspects of the host. The objective was verifying the relationship between SNPs 2029 and 2258 of the TLR-2 gene and leprosy. Blood samples from 127 individuals were analyzed: 45 patients, being 34 multibacillary (MB) and 11 paucibacillary (PB) and 82 contacts, in the municipalities of the State of Pará-Brazil. SNPs 2029 and 2258 of the TLR-2 gene were genotyped by sequencing on the ABI 3130 Genetic Analyzer (Applied Biosystems), analyzed using Fisher’s exact test. Distribution of SNP 2029 genotypes: all MB individuals presented the C/C genotype and the mutant (C/T) genotype was observed in contacts and PB. Alleles: all MB individuals presented only C allele and the mutant allele (T) was observed in contacts and PB. SNP 2258 genotypes: 79 contacts had G/G genotype and only 3 had G/A genotype, the MB group had only G/G genotype and the PB group was predominant G/G, with only 1 G/A genotype. Alleles: all MB individuals had allele G and the mutant allele (A) was observed in contacts and PB. The association between the SNPs and the susceptibility or protection to leprosy was not observed.
KeywordsPolymorphismToll-Like ReceptorsLeprosy
Jin, S.-H., Ahn, K.J. and An, S. (2018) Importance of the Immune Response to Mycobacterium leprae in the Skin. Biomedical Dermatology, 2, Article No. 1. https://doi.org/10.1186/s41702-017-0012-5
Ribeiro, M.D., Silva, J.C. and Oliveira, S. (2018) Estudo epidemiológico da hanseníase no Brasil: Reflexão sobre as metas de eliminação. Revista Panamericana de Salud Publica, 42, 1-7. https://doi.org/10.26633/RPSP.2018.42
White, C. and Franco-Paredes, C. (2015) Leprosy in the 21st Century. Clinical Microbiology Reviews, 28, 80-94. https://doi.org/10.1128/CMR.00079-13
Sauer, M.E.D., Salomão, H., Ramos, G.B., D’Espindula, H.R.S., Rodrigues, R.S.A., Macedo, W.C., et al. (2015) Genetics of Leprosy: Expected and Unexpected Developments and Perspectives. Clinics in Dermatology, 33, 99-107. https://doi.org/10.1016/j.clindermatol.2014.10.001
Mory, D.B., Gabbay, M.A.L., Rocco, E.R., Kasamatsu, T., Crispim, F., Miranda, W.L., et al. (2016) High Frequency of Vitamin D Receptor Gene Polymorphism FokI in Brazilian Type 1 Diabetes Mellitus Patients with Clinical Autoimmune Thyroid Disease. Diabetology & Metabolic Syndrome, 8, 29. https://doi.org/10.1186/s13098-016-0145-5
Fonseca, A.B.L., Simon, M.V., Cazzaniga, R.A., de Moura, T.R., de Almeida, R.P., Duthie, M.S., et al. (2017) The Influence of Innate and Adaptive Immune Responses on the Differential Clinical Outcomes of Leprosy. Infectious Diseases of Poverty, 6, 5. https://doi.org/10.1186/s40249-016-0229-3
Pinheiro, R.O., Schmitz, V., Silva, B.J.A., Dias, A.A., de Souza, B.J., de Mattos Barbosa, M.G., et al. (2018) Innate Immune Responses in Leprosy. Frontiers in Immunology, 9, 518. https://doi.org/10.3389/fimmu.2018.00518
Santana, N.L., Rêgo, J.L., Oliveira, J.M., Almeida, L.F., Braz, M., Machado, L.M.M., et al. (2017) Polymorphisms in Genes TLR1, 2 and 4 Are Associated with Differential Cytokine and Chemokine Serum Production in Patients with Leprosy. Memórias do Instituto Oswaldo Cruz, 112, 260-268. https://doi.org/10.1590/0074-02760160366
Bolz, M. and Ernst, J.D. (2017) Fishing for Answers in Human Mycobacterial Infections. Immunity, 47, 395-397. https://doi.org/10.1016/j.immuni.2017.09.005
Souza, E.A., Ferreira, A.F., Boigny, R.N., Alencar, C.H., Heukelbach, J., Martins-Melo, F.R., et al. (2018) Leprosy and Gender in Brazil: Trends in an Endemic Area of the Northeast Region, 2001-2014. Revista de Saude Publica, 52, 20. https://doi.org/10.11606/S1518-8787.2018052000335
Prevedello, F.C. and Mira, M.T. (2007) Hanseníase: Uma doença genética? Anais Brasileiros de Dermatologia, 82, 451-459. https://doi.org/10.1590/S0365-05962007000500009
Casanova, J.-L., Abel, L. and Quintana-Murci, L. (2011) Human TLRs and IL-1Rs in Host Defense: Natural Insights from Evolutionary, Epidemiological, and Clinical Genetics. Annual Review of Immunology, 29, 447-491. https://doi.org/10.1146/annurev-immunol-030409-101335
Zhang, H., Li, D., Zhao, L., Fleming, J., Lin, N., Wang, T., et al. (2013) Genome Sequencing of 161 Mycobacterium tuberculosis Isolates from China Identifies Genes and Intergenic Regions Associated with Drug Resistance. Nature Genetics, 45, 1255-1260. https://doi.org/10.1038/ng.2735
Van der Graaf, C., Kullberg, B.J., Joosten, L., Verver-Jansen, T., Jacobs, L., Van der Meer, J.W.M., et al. (2005) Functional Consequences of the Asp299Gly Toll-Like Receptor-4 Polymorphism. Cytokine, 30, 264-268. https://doi.org/10.1016/j.cyto.2005.02.001
Ma, M., Xie, L., Wu, S., Tang, F., Li, H., Zhang, Z., et al. (2010) Toll-Like Receptors, Tumor Necrosis Factor-α, and Interleukin-10 Gene Polymorphisms in Risk of Pulmonary Tuberculosis and Disease Severity. Human Immunology, 71, 1005-1010. https://doi.org/10.1016/j.humimm.2010.07.009
Sánchez, D., Lefebvre, C., Rioux, J., García, L.F. and Barrera, L.F. (2012) Evaluation of Toll-Like Receptor and Adaptor Molecule Polymorphisms for Susceptibility to Tuberculosis in a Colombian Population. International Journal of Immunogenetics, 39, 216-223. https://doi.org/10.1111/j.1744-313X.2011.01077.x
Sigmund, C.D. (2000) Viewpoint: Are Studies in Genetically Altered Mice Out of Control? Arteriosclerosis, Thrombosis, and Vascular Biology, 20, 1425-1429. https://doi.org/10.1161/01.ATV.20.6.1425
Johnson, K.R., Zheng, Q.Y. and Noben-Trauth, K. (2006) Strain Background Effects and Genetic Modifiers of Hearing in Mice. Brain Research, 1091, 79-88. https://doi.org/10.1016/j.brainres.2006.02.021
Doetschman, T. (2009) Influence of Genetic Background on Genetically Engineered Mouse Phenotypes. Methods in Molecular Biology, 530, 423-433. https://doi.org/10.1007/978-1-59745-471-1_23
Texereau, J., Chiche, J.-D., Taylor, W., Choukroun, G., Comba, B. and Mira, J.-P. (2005) The Importance of Toll-Like Receptor 2 Polymorphisms in Severe Infections. Clinical Infectious Diseases, 41, S408-S415. https://doi.org/10.1086/431990
Kang, T.J. and Chae, G.T. (2001) Detection of Toll-Like Receptor 2 (TLR2) Mutation in the Lepromatous Leprosy Patients. FEMS Immunology and Medical Microbiology, 31, 53-58. https://doi.org/10.1111/j.1574-695X.2001.tb01586.x
Malhotra, D., Relhan, V., Reddy, B.S.N. and Bamezai, R. (2005) TLR2 Arg677Trp Polymorphism in Leprosy: Revisited. Human Genetics, 116, 413-415. https://doi.org/10.1007/s00439-004-1249-9
Mikita, N., Kanazawa, N., Ozaki, M., Kosaka, M., Ishii, N., Nishimura, H., et al. (2009) No Involvement of Non-Synonymous TLR2 Polymorphisms in Japanese Leprosy Patients. Journal of Dermatological Science, 54, 48-49. https://doi.org/10.1016/j.jdermsci.2008.11.001
Lorenz, E., Mira, J.P., Cornish, K.L., Arbour, N.C. and Schwartz, D.A. (2000) A Novel Polymorphism in the Toll-Like Receptor 2 Gene and Its Potential Association with Staphylococcal Infection. Infection and Immunity, 68, 6398-6401. https://doi.org/10.1128/IAI.68.11.6398-6401.2000
HapMap. (n.d.) The International HapMap Project. Probe (Lond). https://www.ncbi.nlm.nih.gov/probe/docs/projhapmap
Naveca, R.H.B. (2014) Influência De Polimorfismos Dos Genes Tlr (Toll-Like Receptors) Sobre a Tuberculose em uma população da amazônia. Instituto Nacional de Pesquisas da Amazônia INPA.
Ogus, A.C., Yoldas, B., Ozdemir, T., Uguz, A., Olcen, S., Keser, I., et al. (2004) The Arg753Gln Polymorphism of the Human Toll-Like Receptor 2 Gene in Tuberculosis Disease. European Respiratory Journal, 23, 219-223. https://doi.org/10.1183/09031936.03.00061703
Bakker, M.I., Hatta, M., Kwenang, A., Van Mosseveld, P., Faber, W.R., Klatser, P.R., et al. (2006) Risk Factors for Developing Leprosy—A Population-Based Cohort Study in Indonesia. Leprosy Review, 77, 48-61.
Lima, L.N.G.C., Frota, C.C., Mota, R.M.S., Almeida, R.L.F., Pontes, M.A.A., Gonçalves, H.S., et al. (2015) Widespread Nasal Carriage of Mycobacterium lepraeamong a Healthy Population in a Hyperendemic Region of Northeastern Brazil. Memórias do Instituto Oswaldo Cruz, 110, 898-905. https://doi.org/10.1590/0074-02760150178