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Human genetics of common mycobacterial infections

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Abstract

There is increasing interest in and understanding of the role of human genetic factors controlling susceptibility/resistance to infectious diseases. This is of particular importance for the two most common mycobacterial infections, tuberculosis and leprosy, because this will allow a genetic dissection of antimycobacterial immunity and should open new fields of preventive and therapeutic measures. In this review we will initially discuss various methods of genetic epidemiology that have been and are being developed to identify human genes controlling infectious diseases, and then illustrate the findings obtained in the numerous studies performed in tuberculosis and leprosy. Although the most convincing results were observed for HLA-DR2 and NRAMP1 (or a closely linked gene) in pulmonary tuberculosis and leprosy subtypes and for a 10p13 locus in paucibacillary leprosy, the molecular basis of their effects remains to be established.

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References

  1. Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC: Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA 1999;282:677–686.

    Article  PubMed  CAS  Google Scholar 

  2. Bloom B: Tuberculosis: Pathogenesis, Protection and Control. ASM Press, Washington DC, 1994.

    Google Scholar 

  3. WHO: Leprosy-global situation. Wkly Epidemiol Rec 2000;75:226–231.

    Google Scholar 

  4. van Beers SM, de Wit MY, Klatser PR: The epidemiology of Mycobacterium leprae: recent insight. FEMS Microbiol Lett 1996;136:221–230.

    Article  PubMed  Google Scholar 

  5. van der Werf TS, van der Graaf WT, Tappero JW, Asiedu K: Mycobacterium ulcerans infection. Lancet 1999;354:1013–1018.

    Article  PubMed  Google Scholar 

  6. WHO: Buruli ulcer. Wkly Epidemiol Rec 2000;75: 106–108.

    Google Scholar 

  7. Bloom BR, Small PM: The evolving relation between humans and Mycobacterium tuberculosis. N Engl J Med 1998;338:677–678.

    Article  PubMed  CAS  Google Scholar 

  8. Jacobson RR, Krahenbuhl JL: Leprosy. Lancet 1999;353: 655–660.

    Article  PubMed  CAS  Google Scholar 

  9. Gooding TM, Johnson PD, Campbell DE, Hayman JA, Hartland EL, Kemp AS, Robins-Browne RM, et al.: Immune response to infection with Mycobacterium ulcerans. Infect Immun 2001;69:1704–1707.

    Article  PubMed  CAS  Google Scholar 

  10. McLeod R, Buschman E, Arbuckle LD, Skamene E: Immunogenetics in the analysis of resistance to intracellular pathogens. Curr Opin Immunol 1995;7: 539–551.

    Article  PubMed  CAS  Google Scholar 

  11. Buu N, Sanchez F, Schurr E: The Bcg host-resistance gene. Clin Infect Dis 2000;31 Suppl 3:S81-S85.

    Article  PubMed  CAS  Google Scholar 

  12. Casanova JL, Abel L: Genetic dissection of immunity tomycobacteria: the Human Model. Annu Rev Immunol 2002;20: 581–620.

    Article  PubMed  CAS  Google Scholar 

  13. Dupuis S, Doffinger R, Picard C, Fieschi C, Altare F, Jouanguy E, Abel L, et al.: Human interferon-gammamediated immunity is a genetically controlled continuous trait that determines the outcome of mycobacterial invasion. Immunol Rev 2000;178:129–137.

    Article  PubMed  CAS  Google Scholar 

  14. Stead WW: Genetics and resistance to tuberculosis. Could resistance be enhanced by genetic engineering? Ann Intern Med 1992;116:937–941.

    PubMed  CAS  Google Scholar 

  15. Stead WW: The origin and erratic global spread of tuberculosis. How the past explains the present and is the key to the future. Clin Chest Med 1997;18:65–77.

    Article  PubMed  CAS  Google Scholar 

  16. Comstock GW: Tuberculosis in twins: a re-analysis of the Prophit survey. Am Rev Respir Dis 1978;117: 621–624.

    PubMed  CAS  Google Scholar 

  17. Chakravartti MR, Vogel FA: A twin study of leprosy. Top Hum Genet 1973;1:1–123.

    Google Scholar 

  18. Abel L, Demenais F: Detection of major genes for susceptibility to leprosy and its subtypes in a Caribbean island: Desirade island. Am J Hum Genet 1988; 42:256–266.

    PubMed  CAS  Google Scholar 

  19. Abel L, Vu DL, Oberti J, Nguyen VT, Van VC, Guilloud-Bataille M, Schurr E, et al.: Complex segregation analysis of leprosy in southern Vietnam. Genet Epidemiol 1995;12:63–82.

    Article  PubMed  CAS  Google Scholar 

  20. Khoury MJ, Beaty TH, Cohen BH: Fundamentals of Genetic Epidemiology. Oxford University Press, New York, 1993.

    Google Scholar 

  21. Lander ES, Schork NJ: Genetic dissection of complex traits. Science 1994;265:2037–2048.

    Article  PubMed  CAS  Google Scholar 

  22. Abel L, Dessein AJ: Genetic epidemiology of infectious diseases in humans; design of population-based studies. Emerg Infect Dis 1998;4:593–603.

    Article  PubMed  CAS  Google Scholar 

  23. Dib C, Faure S, Fizames C, Samson D, Drouot N, Vignal A, Millasseau P, et al.: A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature 1996;380:152–154.

    Article  PubMed  CAS  Google Scholar 

  24. Wang DG, Fan JB, Siao CJ, Berno A, Young P, Sapolsky R, Ghandour G, et al.: Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. Science 1998;280: 1077–1082.

    Article  PubMed  CAS  Google Scholar 

  25. Kruglyak L: Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nat Genet 1999;22:139–144.

    Article  PubMed  CAS  Google Scholar 

  26. Abel L, Casanova JL: Genetic predisposition to clinical tuberculosis: bridging the gap between simpleand complex inheritance. Am J Hum Genet 2000;67:274–277.

    Article  PubMed  CAS  Google Scholar 

  27. Ott J: Analysis of Human Genetic Linkage. Johns Hopkins University Press, Baltimore, 1999.

    Google Scholar 

  28. Morton N: Sequential tests for the detection of linkage. Am J Hum Genet 1955;7:277–318.

    PubMed  CAS  Google Scholar 

  29. Clerget-Darpoux F, Bonaiti-Pellie C, Hochez J: Effects of misspecifying genetic parameters in lod score analysis. Biometrics 1986;42:393–399.

    Article  PubMed  CAS  Google Scholar 

  30. Lander E, Kruglyak L: Genetic dissection of complex traits: guide lines for interpreting and reporting linkage results. Nat Genet 1995;11:241–247.

    Article  PubMed  CAS  Google Scholar 

  31. MacLean CJ, Bishop DT, Sherman SL, Diehl SR: Distribution of lod scores under uncertain mode of inheritance. Am J Hum Genet 1993;52:354–361.

    PubMed  CAS  Google Scholar 

  32. Risch N: Linkage strategies for genetically complex traits. III. The effect of marker polymorphism on analysis of affected relative pairs. Am J Hum Genet 1990;46:242–253.

    PubMed  CAS  Google Scholar 

  33. Abel L, Muller-Myhsok B: Robustness and power of the maximum-likelihood-binomial and maximum-likelihood-score methods, in multipoint linkage analysis of affected-sibshipdata. Am J Hum Genet 1998;63:638–647.

    Article  PubMed  CAS  Google Scholar 

  34. Feingold E: Methods for linkage analysis of quantitative trait loci in humans. Theor Popul Biol 2001;60:167–180.

    Article  PubMed  CAS  Google Scholar 

  35. Feingold E: Regression-based quantitative-trait-locus mapping in the 21 st century. Am J Hum Genet 2002;71: 217–222.

    Article  PubMed  CAS  Google Scholar 

  36. Elston RC: Methods of linkage analysis-and the assumptions underlying them. Am J Hum Genet 1998;63: 931–934.

    Article  PubMed  CAS  Google Scholar 

  37. Rao DC: CAT scans, PET scans, and genomic scans. Genet Epidemiol 1998;15:1–18.

    Article  PubMed  CAS  Google Scholar 

  38. Sawcer S, Jones HB, Judge D, Visser F, Compston A, Goodfellow PN, Clayton D: Empirical genomewide significance levels established by whole genome simulations. Genet Epidemiol 1997;14:223–229.

    Article  PubMed  CAS  Google Scholar 

  39. Spielman RS, McGinnis RE, Ewens WJ: Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 1993;52:506–516.

    PubMed  CAS  Google Scholar 

  40. Spielman RS, Ewens WJ: A sibship test for linkage in the presence of association: the sib transmission/disequilibrium test. Am J Hum Genet 1998;62:450–458.

    Article  PubMed  CAS  Google Scholar 

  41. Knapp M: The transmission/disequilibrium test and parental-genotype reconstruction: the reconstruction-combined transmission/disequilibrium test. Am J Hum Genet 1999;64:861–870.

    Article  PubMed  CAS  Google Scholar 

  42. Lake SL, Blacker D, Laird NM: Family-based tests of association in the presence of linkage. Am J Hum Genet 2000;67:1515–1525.

    Article  PubMed  CAS  Google Scholar 

  43. Horvath S, Xu X, Laird NM: The family based association test method: strategies for studying general genotype-phenotype associations. Eur J Hum Genet 2001;9:301–306.

    Article  PubMed  CAS  Google Scholar 

  44. Abecasis GR, Cardon LR, Cookson WO: A general test of association for quantitative traits in nuclear families. Am J Hum Genet 2000;66:279–292.

    Article  PubMed  CAS  Google Scholar 

  45. Alcais A, Abel L: Removing phenotypic distribution assumptions from tests of linkage disequilibrium for quantitativetraits. Gen Epidemiol 2003;24(3):191–193.

    Article  Google Scholar 

  46. Rabinowitz D: A transmission disequilibrium test for quantitative trait loci. Hum Hered 1997;47:342–350.

    PubMed  CAS  Google Scholar 

  47. Risch N, Merikangas K: The future of genetic studies of complex human diseases. Science 1996;273: 1516–1517.

    Article  PubMed  CAS  Google Scholar 

  48. Muller-Myhsok B, Abel L: Genetic analysis of complex diseases. Science 1997;275:1328–1329.

    PubMed  CAS  Google Scholar 

  49. Abel L, Muller-Myhsok B: Maximum-likelihood expression of the transmission/disequilibrium test and power considerations. Am J Hum Genet 1998;63:664–667.

    Article  PubMed  CAS  Google Scholar 

  50. Lonjou C, Collins A, Morton NE: Allelic association between marker loci. Proc Natl Acad Sci USA 1999; 96:1621–1626.

    Article  PubMed  CAS  Google Scholar 

  51. Stephens JC, Schneider JA, Tanguay DA, Choi J, Acharya T, Stanley SE, Jiang R, et al.: Haplo-type variation and linkage disequilibrium in 313 human genes. Science 2001;293:489–493.

    Article  PubMed  CAS  Google Scholar 

  52. Reich DE, Cargill M, Bolk S, Ireland J, Sabeti PC, Richter DJ, Lavery T, et al.: Linkage disequilibrium in the human genome. Nature 2001;411:199–204.

    Article  PubMed  CAS  Google Scholar 

  53. Flynn JL, Chan J: Immunology of tuberculosis. Annu Rev Immunol 2001;19:93–129.

    Article  PubMed  CAS  Google Scholar 

  54. Kaufmann SH: How can immunology contribute to the control of tuberculosis? Nat Rev Immunol 2001;1:20–30.

    Article  PubMed  CAS  Google Scholar 

  55. Stem LJ, Brown JH, Jardetzky TS, Gorga JC, Urban RG, Strominger JL, Wiley DC: Crystalstructure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature 1994;368:215–221.

    Article  Google Scholar 

  56. Goldfeld AE, Delgado JC, Thim S, Bozon MV, Uglialoro AM, Turbay D, Cohen C, et al.: Association of an HLA-DQ allele with clinical tuberculosis. JAMA 1998; 279:226–228.

    Article  PubMed  CAS  Google Scholar 

  57. Zerva L, Cizman B, Mehra NK, Alahari SK, Murali R, Zmijewski CM, Kamoun M, et al.: Arginine at positions 13 or 70–71 in pocket 4 of HLA-DRB1 alleles is associated with susceptibility to tuberculoid leprosy. J Exp Med 1996;183:829–836.

    Article  PubMed  CAS  Google Scholar 

  58. Bothamley GH, Beck JS, Schreuder GM, D'Amaro J, de Vries RR, Kardjito T, Ivanyi J: Association of tuberculosis and M. tuberculosis-specific antibody levels with HLA. J Infect Dis 1989;159:549–555.

    PubMed  CAS  Google Scholar 

  59. Brahmajothi V, Pitchappan RM, Kakkanaiah VN, Sashidhar M, Rajaram K, Ramu S, Palanimurugan K, et al.: Association of pulmonary tuberculosis and HLA in south India. Tubercle 1991;72:123–132.

    Article  PubMed  CAS  Google Scholar 

  60. Rajalingam R, Mehra NK, Jain RC, Myneedu VP, Pande JN: Polymerase chain reaction-based sequence-specific oligonucleotide hybridization analysis of HLA class II antigens in pulmonary tuberculosis: relevance to chemotherapy and disease severity. J Infect Dis 1996;173:669–676.

    PubMed  CAS  Google Scholar 

  61. Singh SP, Mehra NK, Dingley HB, Pande JN, Vaidya MC: Human leukocyte antigen (HLA)-linked control of susceptibility to pulmomary tuberculosis and association with HLA-DR types. J Infect Dis 1983;148: 676–681.

    PubMed  CAS  Google Scholar 

  62. Hawkins BR, Higgins DA, Chan SL, Lowrie DB, Mitchison DA, Girling DJ: HLA typing in the Hong Kong Chest Service/British Medical Research Council study of factors associated with the breakdown to active tuberculosis of inactive pulmonary lesions. Am Rev Respir Dis 1988;138:1616–1621.

    PubMed  CAS  Google Scholar 

  63. Cox RA, Downs M, Neimes RE, Ognibene AJ, Yamashita TS, Ellner JJ: Immunogenetic analysis of human tuberculosis. J Infect Dis 1988;158:1302–1308.

    PubMed  CAS  Google Scholar 

  64. Sanjeevi CB, Narayanan PR, Prabakar R, Charles N, Thomas BE, Balasubramaniam R, Olerup O: No association or linkage with HLA-DR or-DQ genes in south Indians with pulmonary tuberculosis. Tuber Lung Dis 1992;73:280–284.

    Article  PubMed  CAS  Google Scholar 

  65. Schreuder GM, Hurley CK, Marsh SG, Lau M, Maiers M, Kollman C, Noreen H: The HLA dictionary 1999: a summary of HLA-A-B,-C,-DRB1/3/4/5,-DQB1 alleles and their association with serologically defined HLA-A,-B,-C,-DR and-DQ antigens. Tissue Antigens 1999;54:409–437.

    Article  PubMed  CAS  Google Scholar 

  66. Mehra NK, Rajalingam R, Mitra DK, Taneja V, Giphart MJ: Variants of HLA-DR2/DR51 group haplotypes and susceptibility to tuberculoid leprosy and pulmonary tuberculosis in Asian Indians. Int J Lepr Other Mycobact Dis 1995;63:241–248.

    PubMed  CAS  Google Scholar 

  67. Ravikumar M, Dheenadhayalan V, Rajaram K, Lakshmi SS, Kumaran PP, Paramasivan CN, Balakrishnan K, et al.: Association of HLA-DRB1, DQB1 and DPB1 alleles with pulmonary tuberculosis in south India. Tuber Lung Dis 1999;79:309–317.

    Article  PubMed  CAS  Google Scholar 

  68. Teran-Escandon D, Teran-Ortiz L, Camarena-Olvera A, Gonzalez-Avila G, Vaca-Marin MA, Granados J, Selman M: Human leukocyte antigen-associated susceptibility to pulmonary tuberculosis: molecular analysis of class II alleles by DNA amplification and oligonucleotide hybridization in Mexican patients. Chest 1999;115:428–433.

    Article  PubMed  CAS  Google Scholar 

  69. Ottenhoff TH, de Vries RR: HLA class 11 immune response and suppression genes in leprosy. Int J Lepr Other Mycobact Dis 1987;55:521–534.

    PubMed  CAS  Google Scholar 

  70. Meyer CG, May J, Stark K: Human leukocyte antigens in tuberculosis and leprosy. Trends Microbiol 1998; 6:148–154.

    Article  PubMed  CAS  Google Scholar 

  71. de Vries RR, Mehra NK, Vaidya MC, Gupte MD, Meera Khan P, Van Rood JJ: HLA-linked control of susceptibility to tuberculoid leprosy and association with HLA-DR types. Tissue Antigens 1980;16:294–304.

    Article  PubMed  Google Scholar 

  72. Dessoukey MW, el-Shiemy S, Sallam T: HLA and leprosy: segregation and linkage study. Int J Dermatol 1996;35:257–264.

    PubMed  CAS  Google Scholar 

  73. Rani R, Fernandez-Vina MA, Zaheer SA, Beena KR, Stastny P: Study of HLA class II alleles by PCR oligotyping in leprosy patients from north India. Tissue Antigens 1993;42:133–137.

    PubMed  CAS  Google Scholar 

  74. de Vries RR, Fat RF, Nijenhuis LE, van Rood JJ: HLA-linked genetic control of host response to Mycobacterium leprae. Lancet 1976;2:1328–1330.

    PubMed  Google Scholar 

  75. Fine PE, Wolf E, Pritchard J, Watson B, Bradley DJ, Festenstein H, Chacko CJ: HLA-linked genes and leprosy: a family study in Karigiri, South India. J Infect Dis 1979;140:152–161.

    PubMed  CAS  Google Scholar 

  76. van Eden W, Gonzalez NM, de Vries RR, Convit J, van Rood JJ: HLA-linked control of predisposition to lepromatous leprosy. J Infect Dis 1985;151:9–14.

    PubMed  Google Scholar 

  77. Xu KY, de Vries RR, Fei HM, van Leeuwen A, Chen RB, Ye GY: HLA-linked control of predisposition to lepromatous leprosy. Int J Lepr Other Mycobact Dis 1985;53:56–63.

    PubMed  CAS  Google Scholar 

  78. Mira MT, Alcais A, di Pietrantonio T, Thuc NV, Phuong MC, Abel L, Schurr E: Segregation of HLA/TNF haplotype is linked to leprosy clinical spectrum in families displaying mixed leprosy subtypes. Genes Immun 2003;4(1):67–73.

    Article  PubMed  CAS  Google Scholar 

  79. Shaw MA, Donaldson IJ, Collins A, Peacock CS, Lins-Lainson Z, Shaw JJ, Ramos F, et al.: Association and linkage of leprosy phenotypes with HLA class II and tumour necrosis factor genes. Genes Immun 2001; 2:196–204.

    Article  PubMed  CAS  Google Scholar 

  80. Allen RD: Polymorphism of the human TNF-alpha promoter-random variation or functional diversity? Mol Immunol 1999;36:1017–1027.

    Article  PubMed  CAS  Google Scholar 

  81. Blackwell JM, Black GF, Peacock CS, Miller EN, Sibthorpe D, Gnananandha D, Shaw JJ, et al.: Immunogenetics of leishmanial and mycobacterial infections: the Belem Family Study. Philos Trans R Soc Lond B Biol Sci 1997;352:1331–1345.

    Article  PubMed  CAS  Google Scholar 

  82. Roy S, McGuire W, Mascie-Taylor CG, Saha B, Hazra SK, Hill AV, Kwiatkowski D: Tumor necrosis factor promoter poly morphism and susceptibility to lepromatous leprosy. J Infect Dis 1997;176:530–532.

    Article  PubMed  CAS  Google Scholar 

  83. Spies T, Bresnahan M, Bahram S, Arnold D, Blanck G, Mellins E, Pious D, et al.: A gene in the human major histocom patibility complex class II region controlling the class I antigen presentation pathway. Nature 1990;348:744–747.

    Article  PubMed  CAS  Google Scholar 

  84. Rajalingam R, Singal DP, Mehra NK: Transporter associated with antigen-processing (TAP) genes and susceptibility to tuberculoid leprosy and pulmonary tuberculosis. Tissue Antigens 1997;49:168–172.

    PubMed  CAS  Google Scholar 

  85. Cellier M, Govoni G, Vidal S, Kwan T, Groulx N, Liu J, Sanchez F, et al.: Human natural resistance-associated macrophage protein: cDNA cloning, chromosomal mapping, genomic organization, and tissue-specific expression. J Exp Med 1994;180:1741–1752.

    Article  PubMed  CAS  Google Scholar 

  86. Vidal SM, Malo D, Vogan K, Skamene E, Gros P: Natural resistance to infection with intracellular parasites: isolation of a candidate for Beg. Cell 1993; 73:469–485.

    Article  PubMed  CAS  Google Scholar 

  87. Vidal SM, Pinner E, Lepage P, Gauthier S, Gros P: Natural resistance to intracellular infections: Nrampl encodes a membrane phosphoglycoprotein absent in macrophages from susceptible (Nrampl D169) mouse strains. J Immunol 1996;157:3559–3568.

    PubMed  CAS  Google Scholar 

  88. North RJ, LaCourse R, Ryan L, Gros P: Consequence of Nrampl deletion to Mycobacterium tuberculosis infection in mice. Infect Immun 1999;67:5811–5814.

    PubMed  CAS  Google Scholar 

  89. Jabado N, Jankowski A, Dougaparsad S, Picard V, Grinstein S, Gros P: Natural resistance to intracellular infections: natural resistance-associated macrophage protein 1 (Nrampl) functions as a pH-dependent manganese transporter at the phagosomal membrane. J Exp Med 2000;192:1237–1248.

    Article  PubMed  CAS  Google Scholar 

  90. Bellamy R, Ruwende C, Corrah T, McAdam KP, Whittle HC, Hill AV: Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans. N Engl J Med 1998;338:640–644.

    Article  PubMed  CAS  Google Scholar 

  91. Ryu S, Park YK, Bai GH, Kim SJ, Park SN, Kang S: 3UTR polymorphisms in the NRAMP1 gene are associated with susceptibility to tuberculosis in Koreans. Int J Tuberc Lung Dis 2000;4:577–580.

    PubMed  CAS  Google Scholar 

  92. Soborg C, Andersen AB, Madsen HO, Kok-Jensen A, Skinhoj P, Garred P: Natural resistance-associated macrophage protein 1 polymorphisms are associated with microscopy-positive tuberculosis. J Infect Dis 2002; 186:517–521.

    Article  PubMed  CAS  Google Scholar 

  93. Cervino AC, Lakiss S, Sow O, Hill AV: Allelic association between the NRAMPI gene and susceptibility to tuberculosis in Guinea-Conakry. Ann Hum Genet 2000;64:507–512.

    Article  PubMed  CAS  Google Scholar 

  94. Gao PS, Fujishima S, Mao XQ, Remus N, Kanda M, Enomoto T, Dake Y, et al.: Genetic variants of NRAMPI and active tuberculosis in Japanese populations. Clin Genet 2000;58:74–76.

    Article  PubMed  CAS  Google Scholar 

  95. Ma X, Dou S, Wright JA, Reich RA, Teeter LD, El Sahly HM, Awe RJ, et al.: 5′ dinucleotide repeat polymorphism of NRAMP1 and susceptibility to tuberculosis among Caucasian patients in Houston, Texas. Int J Tuberc Lung Dis 2002;6:818–823.

    PubMed  CAS  Google Scholar 

  96. El Baghdadi J, Remus N, Benslimane A, Chentoufi M, Abel L, Schurr E: Variants of the human NRAMP1 gene and susceptibility to tuberculosis in Morocco. Int J Tuberc Lung Dis 2003;7(6):599–602.

    PubMed  Google Scholar 

  97. Greenwood CM, Fujiwara TM, Boothroyd LJ, Miller MA, Frappier D, Fanning EA, Schurr E, et al.: Linkage of tuberculosis to chromosome 2q35 loci, including NRAMP1, in a large a boriginal Canadian family. Am J Hum Genet 2000;67:405–416.

    Article  PubMed  CAS  Google Scholar 

  98. Abel L, Sanchez FO, Oberti J, Thuc NV, Hoa LV, Lap VD, Skamene E, et al.: Susceptibility to leprosy is linked to the human NRAMP1 gene. J Infect Dis 1998;177:133–145.

    Article  PubMed  CAS  Google Scholar 

  99. Abel L, Lap VD, Oberti J, Thuc NV, Cua VV, Guilloud-Bataille, M, schurr E, et al.: Complex segregation analysis of leprosy in southern Vietnam. Genet Epidemiol 1995;12:63–82.

    Article  PubMed  CAS  Google Scholar 

  100. Shaw MA, Atkinson S, Dockrell H, Hussain R, Lins-Lainson Z, Shaw J, Ramos F, et al.: An RFLP map for 2q33-q37 from multicase mycobacterial and leishmanial disease families: no evidence for an Lsh/Ity/Bcg gene homologue influencing susceptibility to leprosy. Ann Hum Genet 1993;57:251–271.

    PubMed  CAS  Google Scholar 

  101. Levee G, Liu J, Gicquel B, Chanteau S, Schurr E: Genetic control of susceptibility to leprosy in French Polynesia; no evidence for linkage with markerson telomeric human chromosome 2. Int J Lepr Other Mycobact Dis 1994;62:499–511.

    PubMed  CAS  Google Scholar 

  102. Alcais A, Sanchez FO, Thuc NV, Lap VD, Oberti J, Lagrange PH, Schurr E, 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;181:302–308.

    Article  PubMed  CAS  Google Scholar 

  103. Sao SS, Villarreal-Ramos B, Anjam Khan CM, Hormaeche CE, Blackwell JM: Genetic control of immune response to recombinant antigens carried by anattenuated Salmonella typhimurium vaccine strain: Nramp1 influences T-helper subset responses and protection against leishmanial challenge. Infect Immun 1998; 66:1910–1917.

    Google Scholar 

  104. Yamamura M, Uyemura K, Deans RJ, Weinberg K, Rea TH, Bloom BR, Modlin RL: Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science 1991;254:277–279.

    Article  PubMed  CAS  Google Scholar 

  105. Yamauchi PS, Bleharski JR, Uyemura K, Kim J, Sieling PA, Miller A, Brightbill H, et al.: A role for CD40-CD40 ligand interactions in the generation of type 1 cytokine responses in human leprosy. J Immunol 2000; 165:1506–1512.

    PubMed  CAS  Google Scholar 

  106. Chan TY: Vitamin D deficiency and susceptibility to tuberculosis. Calcif Tissue Int 2000;66:476–478.

    Article  PubMed  CAS  Google Scholar 

  107. Piemonti L, Monti P, Sironi M, Fraticelli P, Leone BE, Dal Cin E, Allavena P, et al.: Vitamin D3 affects differentiation, maturation and function of human monocyte-derived dendritic cells. J Immunol 2000;164:4443–4451.

    PubMed  CAS  Google Scholar 

  108. D'Ambrosio D, Cippitelli M, Cocciolo MG, Mazzeo D, Di Lucia P, Lang R, Sinigaglia F, et al.: Inhibition of IL-12 production by 1,25-dihydroxy vitamin D3. Involvement of NF-kappaB downregulation in transcriptional repression of the p40 gene. J Clin Invest 1998;101:252–262.

    PubMed  Google Scholar 

  109. Griffin MD, Lutz W, Phan VA, Bachman LA, McKean DJ, Kumar R: Dendritic cell modulation by 1 alpha, 25 dihydroxy vitamin D3 and its analogs: a vitamin D receptor-dependent pathway that promotes a persistent state of immaturily in vitro and in vivo. Proc Natl Acad Sci USA 2001;98:6800–6805.

    Article  PubMed  CAS  Google Scholar 

  110. Bellamy R, Ruwende C, Corrah T, McAdam KP, Thursz M, Whittle HC, Hill AV: Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene. J Infect Dis 1999;179:721–724.

    Article  PubMed  CAS  Google Scholar 

  111. Wilkinson RJ, Llewelyn M, Toossi Z, Patel P, Pasvol G, Lalvani A, Wright D, et al.: Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study. Lancet 2000;355:618–621.

    Article  PubMed  CAS  Google Scholar 

  112. Stene LC: Vitamin D deficiency and tuberculosis. Lancet 2000;356:73–74; discussion 74–75.

    Article  PubMed  CAS  Google Scholar 

  113. Roy S, Frodsham A, Saha B, Hazra SK, Mascie-Taylor CG, Hill AV: Association of vitamin D receptor genotype with leprosy type. J Infect Dis 1999;179:187–191.

    Article  PubMed  CAS  Google Scholar 

  114. Morrison NA, Yeoman R, Kelly PJ, Eisman JA: Contribution of trans-acting factor alleles to normal physiological variability: vitamin Dreceptor gene polymorphism and circulating osteocalcin. Proc Natl Acad Sci USA 1992;89:6665–6669.

    Article  PubMed  CAS  Google Scholar 

  115. Neth O, Jack DL, Dodds AW, Holzel H, Klein NJ, Turner MW: Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition. Infect Immun 2000;68:688–693.

    Article  PubMed  CAS  Google Scholar 

  116. Summerfield JA, Sumiya M, Levin M, Tumer MW: Association of mutations in mannose binding protein gene with childhood infection in consecutive hospital series. Bmj 1997;314:1229–1232.

    PubMed  CAS  Google Scholar 

  117. Bellamy R, Ruwende C, McAdam KP, Thursz M, Sumiya M, Summerfield J, Gilbert SC, et al.: Mannose binding protein deficiency is not associated with malaria, hepatitis B carriage nor tuberculosis in Africans. Qim 1998; 91:13–18.

    CAS  Google Scholar 

  118. Selvaraj P, Narayanan PR, Reetha AM: Association of functional mutant homozygotes of the mannose binding protein gene with susceptibility to pulmonary tuberculosis in India. Tuber Lung Dis 1999;79:221–227.

    Article  PubMed  CAS  Google Scholar 

  119. Hoal-Van Helden EG, Epstein J, Victor TC, Hon D, Lewis LA, Beyers N, Zurakowski D, et al.: Mannose-binding protein B allele confers protection against tuberculous meningitis. Pediatr Res 1999;45:459–464.

    Article  PubMed  CAS  Google Scholar 

  120. Garred P, Harboe M, Oettinger T, Koch C, Svejgaard A: Dual role of mannan-binding protein in infections: another case of heterosis? Eur J Immunogenet 1994;21:125–131.

    Article  PubMed  CAS  Google Scholar 

  121. Juffermans NP, Florquin S, Camoglio L, Verbon A, Kolk AH, Speelman P, van Deventer SJ, et al.: Interleukin-1 signalingis essential for host defense during murine pulmonary tuberculosis. J Infect Dis 2000;182:902–908.

    Article  PubMed  CAS  Google Scholar 

  122. Nicklin MJ, Weith A, Duff GW: A physical map of the region encompassing the human interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist genes. Genomics 1994;19:382–384.

    Article  PubMed  CAS  Google Scholar 

  123. Hurme M, Santtila S: IL-1 receptor antagonist (IL-1Ra) plasma levels are co-ordinately regulated by both IL-1 Ra and IL-1 beta genes. Eur J Immunol 1998;28:2598–2602.

    Article  PubMed  CAS  Google Scholar 

  124. Wilkinson RJ, Patel P, Llewelyn M, Hirsch CS, Pasvol G, Snounou G, Davidson RN, et al.: Influence of polymorphism in the genes for the interleukin (IL)-1 receptor antagonist and IL-1 beta on tuberculosis. J Exp Med 1999;189:1863–1874.

    Article  PubMed  CAS  Google Scholar 

  125. Bellamy R, Ruwende C, Corrah T, McAdam KP, Whittle HC, Hill AV: Assessment of the interleukin 1 gene cluster and other candidate gene polymorphisms in host susceptibility to tuberculosis. Tuber Lung Dis 1998;79:83–89.

    Article  PubMed  CAS  Google Scholar 

  126. Rambukkana A: How does Mycobacterium leprae target the peripheral nervous system? Trends Microbiol 2000;8:23–28.

    Article  PubMed  CAS  Google Scholar 

  127. Rambukkana A, Salzer JL, Yurchenco PD, Tuomanen EI: Neural targeting of Mycobacterium leprae mediated by the G domain of the laminin-alpha 2 chain. Cell 1997;88:811–821.

    Article  PubMed  CAS  Google Scholar 

  128. Rambukkana A, Yamada H, Zanazzi G, Mathus T, Salzer JL, Yurchenco PD, Campbell KP, et al.: Role of alpha-dystroglycan as a Schwann cell receptor for Mycobacterium leprae. Science 1998;282:2076–2079.

    Article  PubMed  CAS  Google Scholar 

  129. Wibawa T, Soebono H, Matsuo M: Association of a missense mutation of the laminin alpha2 gene with tuberculoid type of leprosy in Indonesian patients. Trop Med Int Health 2002;7:631–636.

    Article  PubMed  CAS  Google Scholar 

  130. Bellamy R, Beyers N, McAdam KP, Ruwende C, Gie R, Samaai P, Bester D, et al.: Genetic susceptibility to tuberculosis in Africans: a genome-wide scan. Proc Natl Acad Sci USA 2000;97:8005–8009.

    Article  PubMed  CAS  Google Scholar 

  131. Cervino AC, Lakiss S, Sow O, Bellamy R, Beyers N, Hoal-Van Helden E, Van Helden P, et al.: Fine mapping of a putative tuberculosis-susceptibility locus on chromosome 15q11-13 in African families. Hum Mol Genet 2002;11:1599–1603.

    Article  PubMed  CAS  Google Scholar 

  132. Siddiqui MR, Meisner S, Tosh K, Balakrishnan K, Ghei S, Fisher SE, Golding M, et al.: A major susceptibility locus for leprosy in India maps to chromosome 10p13. Nat Genet 2001;27:439–441.

    Article  PubMed  CAS  Google Scholar 

  133. Gomes I, Collins A, Lonjou C, Thomas NS, Wilkinson J, Watson M, Morton N: Hardy-Weinberg quality control. Ann Hum Genet 1999;63:535–538.

    Article  PubMed  CAS  Google Scholar 

  134. Stenger S, Modlin RL: Control of Mycobacterium tuberculosis through mammalian Toll-like receptors. Curr Opin Immunol 2002;14:452–457.

    Article  PubMed  CAS  Google Scholar 

  135. Quackenbush J: Computational analysis of microarray data. Nat Rev Genet 2001;2:418–427.

    Article  PubMed  CAS  Google Scholar 

  136. Horvath S, Baur MP: Future directions of research in statistical genetics. Stat Med 2000;19:3337–3343.

    Article  PubMed  CAS  Google Scholar 

  137. Casanova JL, Abe LL: The human model: a forward genetic dissection of immunity to infection in natural conditions. Nat Rev Immunol, in press.

  138. Mira MT, Alcais A, Van Thuc N, Thai VH, Huong NT, Ba NN, et al.: Chromosome 6q25 is linked to susceptibility to leprosy ina Vietnamese population. Nat Genet 2003;33:412–415.

    Article  PubMed  CAS  Google Scholar 

  139. Bochud PY, Hawn TR, and Aderem A: Cutting edge: a Toll-like receptor2 polymorphism thatisassociated with lepromatous leprosy is unable to mediate mycobacterial signaling. J Immunol 2003;170:3451–3454.

    PubMed  CAS  Google Scholar 

  140. Krutzik SR, Ochoa MT, Sieling PA, Uematsu S, Ng YW, Legaspi A, et al.: Activation and regulation of Toll-like receptors 2 and 1 in human leprosy. Nat Med 2003;9:525–532.

    Article  PubMed  CAS  Google Scholar 

  141. Bleharski JR, Li H, Meinken C, Graeber TG, Ochoa MT, Yamamura M, et al.: Use of genetic profiling in leprosy to discriminate clinical forms of the disease. Science 2003;301:1527–1530.

    Article  PubMed  CAS  Google Scholar 

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  1. Laurent Abel

    Present address: Laboratory of Human Genetics of Infectious Diseases, INSERM U550, Necker Medical School, University René Descartes, 156, Rue de Vaugirard, 75015, Paris, France, EU

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  1. Laboratory of Human Genetics of Infectious Diseases, INSERM U550, Necker Medical School, University René Descartes, 156, Rue de Vaugirard, 75015, Paris, France, EU

    Natascha Remus & Alexandre Alcaïs

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Remus, N., Alcaïs, A. & Abel, L. Human genetics of common mycobacterial infections. Immunol Res 28, 109–129 (2003). https://doi.org/10.1385/IR:28:2:109

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