Genética humana na susceptibilidade à hanseníase

Autores

  • Vânia Nieto Brito de Souza Doutor em Biologia Molecular. Pesquisador Científico do Instituto Lauro de Souza Lima.
  • Ana Carla Pereira Doutor em Ciências Farmacêuticas. Pesquisador Científico do Instituto Lauro de Souza Lima.

DOI:

https://doi.org/10.47878/hi.2007.v32.35199

Palavras-chave:

hanseníase, polimorfismo de um único nucleotídeo, susceptibilidade genética

Resumo

Dados de investigações familiares, de estudos com gêmeos e da genômica do Mycobacterium leprae, bem como observações sobre a epidemiologia da hanseníase, têm apontado a importância da genética humana como determinante do curso da doença desde a resistência à dicotomia imunológica que definem os pólos tuberculóide e virchowiano. Nesse contexto, estudos de varredura genômica e de associação têm apontado algumas regiões genômicas cujas variações são candidatas a fatores de risco para a doença. Entretanto, as associações já descritas são discretas e não se replicam em todos os estudos, o que evidencia a distinção entre os fatores de risco para diferentes populações, além de divergências nos desenhos destes estudos, como causadores destas controvérsias. Assim, esta revisão tem o propósito de compilação dos dados já descritos para as diversas regiões genômicas humanas que devem participar do controle genético da hanseníase.

Referências

1 Pallamary P. Translation of Gerhard Armauer Hansen. Spedalskhedens Aarsager [causes of leprosy]. Int J Lepr 1955; 23: 307-309.
2 Beiguelman, B. Some remarks on the genetics of leprosy resistance. Acta Genet Med Gemellol 1968;17: 584-594.
3 Ávila JL, Convit J. Studies on cellular immunity in leprosy. I Lysossomal enzymes. Int J Leprosy 1970;38(4): 359-64.
4 Modlin RL. Th1-Th2 paradigm: Insights from Leprosy. J Invest Dermatol 1994; 102(6): 828-32.
5 Foss NT. Aspectos Imunológicos da hanseníase. In: Simpósio: Hanseníase. Medicina Ribeirão Preto 1997; 30: 335-9.
6 Goulart IMB, Penha GO, Cunha G. Imunopatologia da hanseníase: a complexidade dos mecanismos da resposta imune do hospedeiro ao Mycobacterium leprae. Rev Soc Bras Méd Trop 2002; 35(4): 365-375.
7 Convit J, Pinardi ME, Rojas FA. Some considerations regardings the immunology of leprosy. Int J Leprosy 1971; 39(2):556-64.
8 Rea TH, Quismorio FP, Harding B et al. Immunologic responses in pacients with lepromatous leprosy. Arch Dermatol 1976; 112(6): 791-800.
9 Nogueira MES, Vilani-Moreno FR, Silva EA et al. Imunologia. In: Noções de Hansenologia. 2ed. Bauru, 2000.
10 Cole ST, Eiglmeier K, Parkhill J et al. Massive gene decay in the leprosy bacillus. Nature 2001; 409(6823): 1007-11.
11 Monot M, Honore N, Garnier T et al. On the origin of leprosy. Science 2005; 308(5724): 1040-2.
12 Blackwell JM, Black GF, Peacock CS et al. Immunogenetics of leishmanial and mycobacterial infections: the Belem Family Study. Philos Trans R Soc Lond B Biol Sci 1997; 352(1359): 1331-45.
13 Blackwell JM. Genetics of host resistance and susceptibility to intramacrophage pathogens: a study of multicase families of tuberculosis, leprosy and leishmaniasis in north-eastern Brazil. Int J Parasitol 1998; 28(1): 21-8.
14 Mira MT, Alcais A, Van Thuc N et al. Chromosome 6q25 is linked to susceptibility to leprosy in a Vietnamese population. Nat Genet 2003; 33(3): 412-5.
15 Shaw MA, Donaldson IJ, Collins A et al. Associat i o n a n d l i n k a g e o f l e p ro s y p h e n ot y p e s w i t h HL A class II and tumour necrosis fac tor genes. Genes Immun 2001; 2(4): 196-204.
16 Miller EN, Jamieson SE, Joberty C et al. Genome-wide scans for leprosy and tuberculosis susceptibility genes in Brazilians. Genes Immun 2004; 5(1):63-7.
17 Todd JR, West BC, McDonald JC. Human leukocyte antigen and leprosy: study in northern Louisiana and review. Rev Infect Dis 1990; 12(1): 63-74.
18 Hegazy AA, Abdel-Hamid IA, Ahmed SF et al. Leprosy in a high-prevalence Egyptian village: epidemiology and risk factors. Int J Dermatol 2002; 41(10): 681-686.
19 Izumi S, Sugiyama K, Matsumoto Y et al. Analysis of the immunogenetic background of Japanese leprosy patients by the HLA system. Vox Sang 1982; 42(5): 243-7.
20 Wang LM, Kimura A, Satoh M et al. HLA linked with leprosy in southern China: HLA-linked resistance alleles to leprosy. Int J Lepr Other Mycobact Dis 1999; 67(4): 403-8.
21 van Eden W, de Vries RR, Mehra NK et al. HLA segregation of tuberculoid leprosy: confirmation of the DR2 marker. J Infect Dis 1980; 141(6): 693-701.
22 van Eden W, Gonzalez NM, Vries RR et al. HLA-linked control of predisposition to lepromatous leprosy. J Infect Dis 1985; 151(1): 9-14.
23 Schauf V, Ryan S, Scollard D et al. Leprosy associated with HLA-DR2 and DQw1 in the population of northern Thailand. Tissue Antigens 1985; 26(4): 243-7.
24 Visentainer JE, Tsuneto LT, Serra MF et al. Association of leprosy with HLA-DR2 in a Southern Brazilian population. Braz J Med Biol Res 1997; 30(1): 51-9.
25 Rani R, Zaheer SA, Mukherjee R. Do human leukocyte antigens have a role to play in differential manifestation of multibacillary leprosy: a study on multibacillary leprosy patients from north India. Tissue Antigens 1992; 40(3): 124-127.
26 Singh M, Balamurugan A, Katoch K et al. Immunogenetics of mycobacterial infections in the North Indian population. Tissue Antigens 2007; 69 Suppl 1: 228-30.
27 Vanderborght PR, Pacheco AG, Moraes ME et al. HLA-DRB1*04 and DRB1*10 are associated with resistance and susceptibility, respectively, in Brazilian and Vietnamese leprosy patients. Genes Immun 2007; 8(4): 320-4.
28 Motta PM, Cech N, Fontan C et al. Role of HLA-DR and HLA-DQ alleles in multibacillary leprosy and paucibacillary leprosy in
the province of Chaco (Argentina). Enferm Infecc Microbiol Clin 2007; 25(10): 627-31.
29 Souza FC, Marcos EV, Ura S et al. Comparative study between the Mitsuda test and the human leukocyte antigens in leprosy patients. Rev Soc Bras Med Trop 2007; 40(2): 188-91.
30 Takata H, Sada M, Ozawa S et al. HLA and mycobacterial infection: increased frequency of B8 in Japanese leprosy. Tissue Antigens 1978; 11(1): 61-4.
31 Kim SJ, Choi IH, Dahlberg S. HLA and leprosy in Koreans. Tissue Antigens 1987; 29(3): 146-53.
32 Greiner J, Schleiermacher E, Smith T. The HLA system and leprosy in Thailand. Hum Genet 1978; 42(2): 201-13.
33 Shankarkumar, U. HLA associations in leprosy patients from Mumbai, India. Lepr Rev 2004; 75(1): 79-85.
34 Steinle A, Li P, Morris DL et al. Interactions of human NKG2D with its ligands MICA, MICB, and homologs of the mouse RAE-1 protein family. Immunogenetics 2001; 53: 279–287.
35 Tosh K, Ravikumar M, Bell JT et al. Variation in MICA and MICB genes and enhanced susceptibility to paucibacillary leprosy in South India. Hum Mol Genet 2006; 15: 2880-2887.
36 Rajalingam R, Singal DP, Mehra NK. Transporter associated with antigen-processing (TAP) genes and susceptibility to tuberculoid leprosy and pulmonary tuberculosis. Tissue Antigens 1997; 49(2): 168-72.
37 Rothe J, Lesslauer W, Lotscher H et al. Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature 1993; 364(6440): 798-802.
38 Beutler, BA. The role of tumor necrosis factor in health and disease. J Rheumatol Suppl 1999; 57: 16-21.
39 Westendorp RG, Langermans JA, Huizinga TW et al. Genetic influence on cytokine production and fatal meningococcal disease. Lancet 1997; 349:170–3.
40 Sarno EN, Santos AR, Jardim MR et al. Pathogenesis of nerve damage in leprosy: genetic polymorphism regulates the production of TNF alpha. Lepr Rev 2000; 71 Suppl: S154-8; discussion S158-60.
41 Roy S, McGuire W, Mascie-Taylor CG et al. Tumor necrosis factor promoter polymorphism and susceptibility to lepromatous leprosy. J Infect Dis 1997; 176(2): 530-2.
42 Vejbaesya S, Mahaisavariya P, Luangtrakool P et al. TNF alpha and NRAMP1 polymorphisms in leprosy. J Med Assoc Thai 2007; 90(6): 1188-92.
43 Santos AR, Almeida AS, Suffys PN et al. Tumor Necrosis Factor Promoter Polymorphism (TNF2) Seemed to Protect Against
Development of severe forms of leprosy In a Pilot Study in Brazilian Patients. Int J Leprosy 2000; 68(3): 325-327.
44 Santos AR, Suffys PN, Vanderborght PR et al. Role of tumor necrosis factor-alpha and interleukin-10 promoter gene polymorphisms in leprosy. J Infect Dis 2002; 186(11): 1687-91.
45 Levée G, Schurr E, Pandey JP.Tumor necrosis factor-alpha, interleukin-1-beta and immunoglobulin (GM and KM) polymorphisms in leprosy. A linkage study. Exp Clin Immunogenet 1997; 14(2): 160-5.
46 Wilson AG, Symons JA, McDowell TL et al. Effects of a polymorphism in the human tumor necrosis factor promoter on transcriptional activation. PNAS 1997; 94: 3195-3199.
47 Louis E, Franchimont D, Piron A et al. Tumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans. Clin Exp Immunol 1998; 113(3): 401-6.
48 Brinkman BM, Zuijdeest D, Kaijzel EL et al. Relevance of the tumor necrosis factor alpha (TNF alpha) -308 promoter polymorphism in TNF alpha gene regulation. J Inflamm 1995; 46(1): 32-41.
49 Somoskovi A, Zissel G, Seitzer U et al. Polymorphisms at position -308 in the promoter region of the TNF-alpha and in the first intron of the TNF-beta genes and spontaneous and lipopolysaccharide-induced TNF-alpha release in sarcoidosis. Cytokine 1999; 11(11): 882-7.
50 Fitness J, Floyd S, Warndorff DK, et al. Large-scale candidate gene study of leprosy susceptibility in the karonga district of northern Malawi. Am J Trop Hyg 2004; 71(3): 330-340.
51 Cardoso CC. Caracterização de polimorfismos de base única em genes candidatos na Hanseníase. [Dissertação]. Rio de Janeiro (RJ): Fundação Oswaldo Cruz; 2006.
52 Alcais A, Alter A, Antoni G et al. Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy. Nat Genet 2007; 39(4): 517-22.
53 Mira MT, Alcais A, Nguyen VT et al. Susceptibility to leprosy is associated with PARK2 and PACRG. Nature 2004; 427(6975): 636-40.
54 Malhotra D, Darvishi K, Lohra M et al. Association study of major risk single nucleotide polymorphisms in the common regulatory region of PARK2 and PACRG genes with leprosy in an Indian population. Eur J Hum Genet 2006; 14(4): 438-42.
55 Schurr E, Alcaïs A, de Léséleuc L et al Genetic predisposition to leprosy: A major gene reveals novel pathways of immunity to Mycobacterium leprae. Semin Immunol 2006; 18(6): 404-410.
56 Lima MC, Pereira GM, Rumjanek FD et al. Immunological cytokine correlates of protective immunity and pathogenesis in leprosy. Scand J Immunol 2000; 51(4): 419-28.
57 Misra N, Murtaza A, Walker B et al. Cytokine profile of circulating T cells of leprosy patients reflects both indiscriminate and polarized T-helper subsets: T-helper phenotype is stable and uninfluenced by related antigens of Mycobacterium leprae. Immunol 1995;86(1): 97.
58 Bienvenu J, Doche C, Gutowski MC et al. Production of proinflammatory cytokines and cytokines involved in the TH1/TH2 balance is modulated by pentoxifylline. J Cardiovasc Pharmacol 1995;25 Suppl 2:S80–4.
59 Lazarus M, Hajeer AH, Turner D et al. Genetic variation in the interleukin 10 gene promoter and systemic lupus erythematosus. J Rheumatol 1997; 24:2314–7.
60 Turner DM, Williams DM, Sankaran D et al. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J
Immunogenet 1997; 24(1): 1-8.
61 Eskdale J, Keijsers V, Huizinga T, et al. Microsatellite alleles and single nucleotide polymorphisms (SNP) combine to form four major haplotype families at the human interleukin-10 (IL-10) locus. Genes Immun 1999; 1(2): 151-5.
62 Gibson AW, Edberg JC, Wu J, et al. Novel single nucleotide polymorphisms in the distal IL-10 promoter affect IL-10 production and enhance the risk of systemic lupus erythematosus. J Immunol 2001; 166(6): 3915-22.
63 Crawley E, Kay R, Sillibourne S et al. Polymorphic haplotypes of the interleukin-10 5’ flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis. Arthritis Rheum 1999; 42(6): 1101–1108.
64 Moraes MO, Pacheco AG, Schonkeren JJM et al. Interleukin-10 promoter single-nucleotide polymorphisms as markers for disease susceptibility and disease severity in leprosy. Genes Immun 2004; 5(7): 592-5.
65 Malhotra D, Darvishi K, Sood S et al IL-10 promoter single nucleotide polymorphisms are significantly associated with resistance to leprosy. Hum Genet 2005; 118(2): 295-300.
66 Ottenhoff THM, Verreck FAW, Lichtenauer-Kaligis EGR et al. Genetics, cytokines and human infectious disease: lessons from weakly phathogenic mycobacteria and salmonella. Nat Genet 2002; 32: 97-105.
67 Langrish CL, McKenzie BS, Wilson NJ, et al. IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunol Rev 2004; 202: 96-105.
68 Huang D, Cancilla MR, Morahan G. Complete primary structure, chromosomal localisation, and definition of polymorphisms of the gene encoding the human interleukin-12 p40 subunit. Genes Immun 2000; 1(8): 515-20.
69 Yilmaz V, Yentur SP, Saruhan-Direskeneli G. IL-12 and IL-10 polymorphisms and their effects on cytokine production. Cytokine 2005; 30(4): 188-94.
70 Morahan G, Kaur G, Singh M et al. Association of variants in the IL12B gene with leprosy and tuberculosis. Tissue Antigens 2007; 69 Suppl 1: 234-6.
71 Akahoshi M, Nakashima H, Miyake K et al. Influence of interleukin-12 receptor B1 polimorphisms on tuberculosis. Hum Genet 2003; 112:237-243.
72 Lee SB, Kim BC, Jin SH et al. Chae Missense mutations of the interleukin-12 receptor beta 1(IL12RB1) and interferongamma receptor 1 (IFNGR1) genes are not associated with susceptibility to lepromatous leprosy in Korea. Immunogenetics 2003; 55(3): 177-81.
73 Ohyama H, Ogata K, Takeuchi K et al. Polymorphism of the 5’ flanking region of the IL-12 receptor ß2 gene partially determines the clinical types of leprosy through impaired transcriptional activity. J Clin Pathol 2005; 58: 740-743.
74 Doffinger R, Altare F, Casanova JL. Genetic heterogeneity of Mendelian susceptibility to mycobacterial infection. Microbes Infect 2000; 2(13):1553-7.
75 Reynard MP, Turner D, Junqueira-Kipnis AP et al. Allele frequencies for an interferon-gamma microsatellite in a population of Brazilian leprosy patients. Eur J Immunogenet 2003; 30(2): 149-51.
76 Lio D, Marino V, Serauto A, et al. Genotype frequencies of the +874TàA single nucleotide polymorphism in the first intron of the interferon-gamma gene in a sample of Sicilian patients affected by tuberculosis. Eur J Immunogenet 2002; 29(5): 371-4.
77 Maderuelo DL, Arnalich F, Serantes R, et al. Interferon- and Interleukin-10 Gene Polymorphisms in Pulmonary Tuberculosis. Am J Respi Crit Care Med 2003; 167: 970-5.
78 Rossouw M, Nel HJK, Cooke GS et al. Association between tuberculosis and a polymorphic NFkappaB binding site in the interferon gamma gene. Lancet 2003; 361(9372): 1871-2.
79 Jouanguy E, Altare F, Lamhamedi S et al. Interferon- Receptor Deficiency in an Infant with Fatal Bacille Calmette Guérin Infection. N Engl J Med 1996; 335: 1956 - 1962.
80 Newport MJ, Huxley CM, Huston S et al. A Mutation in the Interferon- –Receptor Gene and Susceptibility to Mycobacterial Infection. N Engl J Med 1996; 335: 1941 - 1949.
81 Rigby, WF. The immunobiology of vitamin D. Immunol Today, Feb 1988; 9(2): 54-8.
82 Morrison NA, Qi JC, Tokita A et al. Prediction of bone density from vitamin D receptor alleles. Nature 1994; 367(6460): 284-7.
83 Selvaraj P, Chandra G, Jawahar MS et al. Regulatory role of vitamin D receptor gene variants of Bsm I, Apa I, Taq I, and Fok I polymorphisms on macrophage phagocytosis and lymphoproliferative response to mycobacterium tuberculosis antigen in pulmonary tuberculosis. J Clin Immunol 2004; 24(5): 523-32.
84 Jurutka PW, Remus LS, Whitfield GK et al. The Polymorphic N Terminus in Human Vitamin D Receptor Isoforms Influences Transcriptional Activity by Modulating Interaction with Transcription Factor IIB. Mol Endocrinol 2000; 14: 401.
85 Roy S, Frodsham A, Saha B et al. Association of vitamin D receptor genotype with Leprosy type. J Infec Dis 1999; 179: 187-191.
86 Lewis SJ, Baker I, Davey Smith G. Meta-analysis of vitamin D receptor polymorphisms and pulmonary tuberculosis risk. Int J Tuberc Lung Dis. 2005;9(10):1174-7.
87 Takeda KT, Kaisho T, Akira S. Toll-like receptors. Annu Rev Immunol 2003; 21: 335-376.
88 Underhill DM, Ozinsky A, Smith KD et al. Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages. PNAS 1999; 96: 14459-63.
89 Ozinsky A, Underhill DM, Fontenot JD et al. The repertoire for pattern recognition of pathogens by the innate immune
system is defined by cooperation between toll-like receptors. Proc Natl Acad Sci USA. 2000 ; 97(25): 13766-71.
90 Krutzik SR, Ochoa MT, Sieling PA et al. Activation and regulation of Toll-like receptors 2 and 1 in human leprosy. Nat Med. 2003; 9(5): 525-32.
91 Oliveira RB, Ochoa MT, Sieling PA et al. Expression of Toll-like receptor 2 on human Schwann cells: a mechanism of nerve
damage in leprosy. Infect Immun 2003; 71(3): 1427-33. 92 Kang TJ, Chae GT. Detection of Toll-like receptor 2 (TLR2) mutation in the lepromatous leprosy patients. FEMS Immunol Med Microbiol 2001; 31(1): 53-8.
93 Schröder NW, Hermann C, Hamann L et al. High frequency of polymorphism Arg753Gln of the Toll-like receptor-2 gene
detected by a novel allele-specific PCR. J Mol Med 2003; 81(6): 368-72.
94 Alcais A, Mira JL, Casanova JL, et al. Genetic dissection of immunity in leprosy. Curr Opin Immunol 2005;17(1): 44-8.
95 Malhotra D, Relhan V, Reddy BS et al. TLR2 Arg677Trp polymorphism in leprosy: revisited. Hum Genet 2005; 116(5): 413-5.
96 Bochud PY, Hawn TR, Siddiqui MR et al. Toll-Like Receptor 2 (TLR2) Polymorphisms Are Associated with Reversal Reaction in Leprosy. J Infect Dis 2008; 197(2): 253-261.
97 Johnson CM, Lyle EA, Omueti KO et al. Cutting Edge: A Common Polymorphism Impairs Cell Surface Trafficking and Functional Responses of TLR1 but Protects against Leprosy. J Immunol 2007; 178: 7520 - 7524.
98 Ogus AC, Yoldas B, Ozdemir T et al. The Arg753Gln polymorphism of the human Toll-like receptor 2 gene in tuberculosis disease. Eur Respir J 2004; 23: 219-23.
99 Skamene E, Gros P, Forget A et al. Genetic regulation of resistance to intracellular pathogens. Nature 1982; 297(5866): 506-9.
100 Fortier A, Min-Oo G, Forbes J et al. Single gene effects in mouse models of host: pathogen interactions. J Leukoc Biol 2005; 77: 868-877.
101 Abel L, Sanchez F, Thuc NV et al. Linkage of leprosy to the human NRAMP1 gene in Vietnamese families. Braz J Genet 1996; 19: 113.
102 Abel L, Sanchez FO, Oberti J et al. Susceptibility to leprosy is linked to the human NRAMP1 gene. J Infect Dis 1998; 177(1): 133-45.
103 Meisner SJ, Mucklow S, Warner G et al. Association of NRAMP1 polymorphism with leprosy type but not susceptibility to leprosy per se in west Africans. Am J Trop Med Hyg 2001; 65: 733-735.
104 Roger M, Levee G, Chanteau S et al. No evidence for linkage between leprosy susceptibility and the human natural resistance-associated macrophage protein 1 (NRAMP1) gene in French Polynesia. Int J Lepr Other Mycobact Dis 1997; 65(2): 197-202.
105 Alcais A, Sanchez FO, Thuc NV et al. Granulomatous reaction to intradermal injection of lepromin (Mitsuda reaction) is
linked to the human NRAMP1 gene in Vietnamese leprosy sibships. J Infect Dis 2000; 181(1): 302-8.
106 Ferreira FR, Goulart LR, Silva HD et al. Susceptibility to leprosy may be conditioned by an interaction between the NRAMP1
promoter polymorphisms and the lepromin response. Int J Lepr Other Mycobact Dis 2004; 72(4): 457-67.
107 Hatagima A, Opromolla DV, Ura S et al. No evidence of linkage between Mitsuda reaction and the NRAMP1 locus. Int J Lepr
Other Mycobact Dis 2001; 69(2): 99-103.
108 Ranque B, Alter A, Mira M Et al. Genomewide linkage analysis of the granulomatous mitsuda reaction implicates chromosomal regions 2q35 and 17q21. J Infect Dis 2007; 196(8): 1248-1252.
109 Garred P, Harboe M, Oettinger T et al. Dual role of mannanbinding protein in infections: another case of heterosis? Eur J Immunogenet, April 1, 1994; 21(2): 125-31.
110 Dornelles LN, Pereira-Ferrari L, Messias-Reason I. Mannanbinding lectin plasma levels in leprosy: deficiency confers protection against the lepromatous but not the tuberculoid forms. Clin Exp Immunol 2006; 145(3): 463-8.
111 Messias-Reason IJ, Boldt AB, Moraes Braga AC et al. The association between mannan-binding lectin gene polymorphism and clinical leprosy: new insight into an old paradigm. J Infect Dis 2007; 196(9): 1379-85.
112 Jamieson SE, Miller EN, Black GF et al. Evidence for a cluster of genes on chromosome 17q11-q21 controlling susceptibility to tuberculosis and leprosy in Brazilians. Genes Immun 2004; 5(1): 46-57.
113 Araki T, Milbrandt J. Ninjurin a novel adhesion molecule, is induced by nerve injury and promotes axonal growth. Neuron 1996; 17(2): 353-61.
114 Cardoso CC, Martinez AN, Guimaraes PE et al. Ninjurin 1 asp110ala single nucleotide polymorphism is associated with
protection in leprosy nerve damage. J Neuroimmunol 2007; 190(1-2): 131-8.
115 Kaur G, Sachdeva G, Bhutani LK et al. Association of polymorphism at COL3A and CTLA4 loci on chromosome 2q31-33 with the clinical phenotype and in-vitro CMI status in healthy and leprosy subjects: a preliminary study. Hum Genet 1997; 100(1): 43-50.
116 Holopainen PM, Partanen JA. Technical Note: Linkage Disequilibrium and Disease-Associated CTLA4 Gene Polymorphisms. J Immunol 2001; 167: 2457-2458.
117 Siddiqui MR, Meisner S, Tosh K et al. A major susceptibility locus for leprosy in India maps to chromosome 10p13. Nature
genet 2001; 27: 439-41.
118 Tosh K, Meisner S, Siddiqui MR et al. A Region of Chromosome 20 Is Linked to Leprosy Susceptibility in a South Indian Population. J Infect Dis 2002; 186:1190–3.
119 Nair RP, Henseler T, Jenisch S, et al. Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan. Hum Mol Genet 1997; 6:1349–56.
120 Trembath RC, Clough RL, Rosbotham JL, et al. Identification of a major susceptibility locus on chromosome 6p and evidence for further disease loci revealed by a two stage genome-wide search in psoriasis. Hum Mol Genet 1997; 6:813–20.
121 Cookson WO, Ubhi B, Lawrence R, et al. Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci. Nat Genet 2001; 27:372–3.
122 Rajalingam R, Mehra NK, Singal DP. Polymorphism in heat-shock protein 70-1 (HSP70-1) gene promoter region and susceptibility to tuberculoid leprosy and pulmonary tuberculosis in Asian Indians. Indian J Exp Biol 2000; 38(7): 658-662.

Downloads

Publicado

30-06-2007

Como Citar

1.
Souza VNB de, Pereira AC. Genética humana na susceptibilidade à hanseníase. Hansen. Int. [Internet]. 30º de junho de 2007 [citado 7º de dezembro de 2022];32(1):81-93. Disponível em: https://periodicos.saude.sp.gov.br/hansenologia/article/view/35199

Edição

Seção

Artigos de revisão