Mammalian Genome

, Volume 22, Issue 1–2, pp 19–31

Leprosy as a genetic disease

  • Andrea Alter
  • Audrey Grant
  • Laurent Abel
  • Alexandre Alcaïs
  • Erwin Schurr
Article

Abstract

Leprosy (Hansen’s disease) is a human infectious disease whose etiological agent, Mycobacterium leprae, was identified by G. H. A. Hansen in the 19th century. Despite the high efficacy of multidrug therapy (<0.1% annual relapse rate), transmission is persistent. In 2008, approximately 250,000 new cases were reported to the World Health Organization. Clinically, leprosy presents as either the paucibacillary (1–5 lesions) or the multibacillary (>5 lesions) subtype, highly reflective of a Th1 (cell-mediated) or Th2 (humoral) host immune response, respectively. Subsequent to Mycobacterium leprae exposure, epidemiological studies (e.g., twin studies and complex segregation analyses) maintain the importance of host genetics in susceptibility to leprosy. The results of genome-wide analyses (linkage and association) and candidate gene studies suggest an independent genetic control over both susceptibility to leprosy per se and development of clinical subtype. Moreover, the emergence of a shared genetic background between leprosy and several inflammatory/autoimmune diseases suggests that leprosy is a suitable model for studying the genetic architecture and subsequent pathogenesis of both infectious and inflammatory/autoimmune diseases. We provide the example of NOD2 (Crohn’s disease gene) and LTA (myocardial infarction gene) and the implication of a common genetic risk factor between these two diseases and leprosy. The value of leprosy as a model disease therefore extends far beyond this ancient disease to common afflictions of the 21st century.

Supplementary material

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References

  1. Abel L, Demenais F (1988) Detection of major genes for susceptibility to leprosy and its subtypes in a Caribbean island: Desirade island. Am J Hum Genet 42:256–266PubMedGoogle Scholar
  2. Abel L, Vu DL, Oberti J, Nguyen VT, Van VC et al (1995) Complex segregation analysis of leprosy in southern Vietnam. Genet Epidemiol 12:63–82PubMedGoogle Scholar
  3. Abel L, Sanchez FO, Oberti J, Thuc NV, Hoa LV et al (1998) Susceptibility to leprosy is linked to the human NRAMP1 gene. J Infect Dis 177:133–145PubMedGoogle Scholar
  4. Abraham LJ, Kroeger KM (1999) Impact of the -308 TNF promoter polymorphism on the transcriptional regulation of the TNF gene: relevance to disease. J Leukoc Biol 66:562–566PubMedGoogle Scholar
  5. Alcaïs A, Alter A, Antoni G, Orlova M, Nguyen VT et al (2007) Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy. Nat Genet 39:517–522PubMedGoogle Scholar
  6. Ali S, Vollaard A, Widjaja S, Surjadi C, van de Vosse E et al (2006) PARK2/PACRG polymorphisms and susceptibility to typhoid and paratyphoid fever. Clin Exp Immunol 144:425–431PubMedGoogle Scholar
  7. Alter A, Alcais A, Abel L, Schurr E (2008) Leprosy as a genetic model for susceptibility to common infectious diseases. Hum Genet 123:227–235PubMedGoogle Scholar
  8. Alter A, de Leseleuc L, Van Thuc N, Thai VH, Huong NT et al (2010) Genetic and functional analysis of common MRC1 exon 7 polymorphisms in leprosy susceptibility. Hum Genet 127:337–348PubMedGoogle Scholar
  9. Balding J, Kane D, Livingstone W, Mynett-Johnson L, Bresnihan B et al (2003) Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity. Arthritis Rheum 48:1408–1413PubMedGoogle Scholar
  10. Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH et al (2008) Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 40:955–962PubMedGoogle Scholar
  11. Behr MA, Schurr E (2006) Mycobacteria in Crohn’s disease: a persistent hypothesis. Inflamm Bowel Dis 12:1000–1004PubMedGoogle Scholar
  12. Berrington WR, Macdonald M, Khadge S, Sapkota BR, Janer M et al (2010) Common polymorphisms in the NOD2 gene region are associated with leprosy and its reactive states. J Infect Dis 201:1422–1435PubMedGoogle Scholar
  13. Bochud PY, Sinsimer D, Aderem A, Siddiqui MR, Saunderson P et al (2009) Polymorphisms in Toll-like receptor 4 (TLR4) are associated with protection against leprosy. Eur J Clin Microbiol Infect Dis 28:1055–1065PubMedGoogle Scholar
  14. Boraska V, Zeggini E, Groves CJ, Rayner NW, Skrabic V et al (2009) Family-based analysis of tumor necrosis factor and lymphotoxin-alpha tag polymorphisms with type 1 diabetes in the population of South Croatia. Hum Immunol 70:195–199PubMedGoogle Scholar
  15. Casanova JL, Abel L (2007) Human genetics of infectious diseases: a unified theory. EMBO J 26:915–922PubMedGoogle Scholar
  16. Chakravartti M, Vogel F (1973) A twin study on leprosy. In: Becker PE, Lenz W, Vogel F, Wendt GG (eds) Topics in human genetics. Georg Thieme, StuttgartGoogle Scholar
  17. Chaudhury S, Hazra SK, Saha B, Mazumder B, Biswas PC et al (1994) An eight-year field trial on antileprosy vaccines among high-risk household contacts in the Calcutta metropolis. Int J Lepr Other Mycobact Dis 62:389–394PubMedGoogle Scholar
  18. Cobat A, Gallant CJ, Simkin L, Black GF, Stanley K et al (2009) Two loci control tuberculin skin test reactivity in an area hyperendemic for tuberculosis. J Exp Med 206(12):2583–2591PubMedGoogle Scholar
  19. Cobat A, Orlova M, Alcaïs A, Schurr E (2010) Genetics of susceptibility and resistance to infection. In: Kaufmann SHE, Kabelitz D (eds) Immunology of infection (methods in microbiology). Academic Press, New YorkGoogle Scholar
  20. Cole ST, Eiglmeier K, Parkhill J, James KD, Thomson NR et al (2001) Massive gene decay in the leprosy bacillus. Nature 409:1007–1011PubMedGoogle Scholar
  21. Convit J, Sampson C, Zuniga M, Smith PG, Plata J et al (1992) Immunoprophylactic trial with combined Mycobacterium leprae/BCG vaccine against leprosy: preliminary results. Lancet 339:446–450PubMedGoogle Scholar
  22. Cooke G, Hill A (2008) Tuberculosis, leprosy and other mycobacterial diseases. In: McNicholl JM, Hill AVS, Kaslow RA (eds) Genetic susceptibility to infectious diseases. Oxford University Press, New YorkGoogle Scholar
  23. Cooney R, Jewell D (2009) The genetic basis of inflammatory bowel disease. Dig Dis 27:428–442PubMedGoogle Scholar
  24. De La Vega FM, Isaac H, Collins A, Scafe CR, Halldorsson BV et al (2005) The linkage disequilibrium maps of three human chromosomes across four populations reflect their demographic history and a common underlying recombination pattern. Genome Res 15:454–462Google Scholar
  25. Eleftherohorinou H, Wright V, Hoggart C, Hartikainen AL, Jarvelin MR et al (2009) Pathway analysis of GWAS provides new insights into genetic susceptibility to 3 inflammatory diseases. PLoS One 4:e8068PubMedGoogle Scholar
  26. Feitosa MF, Borecki I, Krieger H, Beiguelman B, Rao DC (1995) The genetic epidemiology of leprosy in a Brazilian population. Am J Hum Genet 56:1179–1185PubMedGoogle Scholar
  27. Fitness J, Tosh J, Hill AVS (2002) Genetics of susceptibility to leprosy. Genes Immun 3:441–453PubMedGoogle Scholar
  28. Fulco TO, Lopes UG, Sarno EN, Sampaio EP, Saliba AM (2007) The proteasome function is required for Mycobacterium leprae-induced apoptosis and cytokine secretion. Immunol Lett 110:82–85PubMedGoogle Scholar
  29. Gallant CJ, Malik S, Jabado N, Cellier M, Simkin L et al (2007) Reduced in vitro functional activity of human NRAMP1 (SLC11A1) allele that predisposes to increased risk of pediatric tuberculosis disease. Genes Immun 8:691–698PubMedGoogle Scholar
  30. Greenstein RJ (2003) Is Crohn’s disease caused by a mycobacterium? Comparisons with leprosy, tuberculosis, and Johne’s disease. Lancet Infect Dis 3:507–514PubMedGoogle Scholar
  31. Greenstein RJ, Greenstein AJ (1995) Is there clinical, epidemiological and molecular evidence for two forms of Crohn’s disease? Mol Med Today 1:343–348PubMedGoogle Scholar
  32. Gruenheid S, Gros P (2000) Genetic susceptibility to intracellular infections: Nramp1, macrophage function and divalent cations transport. Curr Opin Microbiol 3:43–48PubMedGoogle Scholar
  33. Gupte M, Vallishayee R, Anantharaman D, Nagaraju B, Sreevatsa et al (1998) Comparative leprosy vaccine trial in south India. Indian J Lepr 70:369–388PubMedGoogle Scholar
  34. Hackam DJ, Rotstein OD, Zhang W, Gruenheid S, Gros P et al (1998) Host resistance to intracellular infection: mutation of natural resistance-associated macrophage protein 1 (Nramp1) impairs phagosomal acidification. J Exp Med 188:351–364PubMedGoogle Scholar
  35. Haile RW, Iselius L, Fine PE, Morton NE (1985) Segregation and linkage analyses of 72 leprosy pedigrees. Hum Hered 35:43–52PubMedGoogle Scholar
  36. Halsall JA, Osborne JE, Pringle JH, Hutchinson PE (2005) Vitamin D receptor gene polymorphisms, particularly the novel A-1012G promoter polymorphism, are associated with vitamin D3 responsiveness and non-familial susceptibility in psoriasis. Pharmacogenet Genomics 15:349–355PubMedGoogle Scholar
  37. Hampe J, Cuthbert A, Croucher PJ, Mirza MM, Mascheretti S et al (2001) Association between insertion mutation in NOD2 gene and Crohn’s disease in German and British populations. Lancet 357:1925–1928PubMedGoogle Scholar
  38. Hansen GA (1875) On the etiology of leprosy. Br Foreign Med-Chir Rev 55:459–489Google Scholar
  39. Hatta M, van Beers SM, Madjid B, Djumadi A, de Wit MY et al (1995) Distribution and persistence of Mycobacterium leprae nasal carriage among a population in which leprosy is endemic in Indonesia. Trans R Soc Trop Med Hyg 89:381–385PubMedGoogle Scholar
  40. Helgadottir A, Manolescu A, Helgason A, Thorleifsson G, Thorsteinsdottir U et al (2006) A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. Nat Genet 38:68–74PubMedGoogle Scholar
  41. Hill AV (2006) Aspects of genetic susceptibility to human infectious diseases. Annu Rev Genet 40:469–486PubMedGoogle Scholar
  42. Hill AV, Allsopp CE, Kwiatkowski D, Anstey NM, Twumasi P et al (1991) Common West African HLA antigens are associated with protection from severe malaria. Nature 352:595–600PubMedGoogle Scholar
  43. Hiroi S, Harada H, Nishi H, Satoh M, Nagai R et al (1999) Polymorphisms in the SOD2 and HLA-DRB1 genes are associated with nonfamilial idiopathic dilated cardiomyopathy in Japanese. Biochem Biophys Res Commun 261:332–339PubMedGoogle Scholar
  44. Holloway JW, Barton SJ, Holgate ST, Rose-Zerilli MJ, Sayers I (2008) The role of LTA4H and ALOX5AP polymorphism in asthma and allergy susceptibility. Allergy 63:1046–1053PubMedGoogle Scholar
  45. Horton R, Wilming L, Rand V, Lovering RC, Bruford EA et al (2004) Gene map of the extended human MHC. Nat Rev Genet 5:889–899PubMedGoogle Scholar
  46. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP et al (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411:599–603PubMedGoogle Scholar
  47. International Leprosy Association (2002) Report of the International Leprosy Association Technical Forum: epidemiology and control. Int J Lepr 70(suppl):1–62Google Scholar
  48. International Multiple Sclerosis Genetics Consortium, Hafler DA, Compston A, Sawcer S, Lander ES et al (2007) Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 357:851–862PubMedGoogle Scholar
  49. Jabado N, Jankowski A, Dougaparsad S, Picard V, Grinstein S et al (2000) Natural resistance to intracellular infections: natural resistance-associated macrophage protein 1 (Nramp1) functions as a pH-dependent manganese transporter at the phagosomal membrane. J Exp Med 192:1237–1248PubMedGoogle Scholar
  50. Jamieson SE, Miller EN, Black GF, Peacock CS, Cordell HJ et al (2004) Evidence for a cluster of genes on chromosome 17q11–q21 controlling susceptibility to tuberculosis and leprosy in Brazilians. Genes Immun 5:46–57PubMedGoogle Scholar
  51. Janeway CA, Travers P, Walport M, Shlomchik M (2001) Immunobiology. Garland Science, New York and LondonGoogle Scholar
  52. Jawaheer D, Li W, Graham RR, Chen W, Damle A et al (2002) Dissecting the genetic complexity of the association between human leukocyte antigens and rheumatoid arthritis. Am J Hum Genet 71:585–594PubMedGoogle Scholar
  53. Jeyanathan M, Boutros-Tadros O, Radhi J, Semret M, Bitton A et al (2007) Visualization of Mycobacterium avium in Crohn’s tissue by oil-immersion microscopy. Microbes Infect 9:1567–1573PubMedGoogle Scholar
  54. Johnson CM, Lyle EA, Omueti KO, Stepensky VA, Yegin O et al (2007) Cutting edge: a common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy. J Immunol 178:7520–7524PubMedGoogle Scholar
  55. Jones L, Moszer I, Cole ST (2001) Leproma: a Mycobacterium leprae genome browser. Lepr Rev 72:470–477PubMedGoogle Scholar
  56. Kabesch M, Peters W, Carr D, Leupold W, Weiland SK et al (2003) Association between polymorphisms in caspase recruitment domain containing protein 15 and allergy in two German populations. J Allergy Clin Immunol 111:813–817PubMedGoogle Scholar
  57. Kang TJ, Chae GT (2001) Detection of Toll-like receptor 2 (TLR2) mutation in the lepromatous leprosy patients. FEMS Immunol Med Microbiol 31:53–58PubMedGoogle Scholar
  58. Kirchheimer WF, Storrs EE (1971) Attempts to establish the armadillo (Dasypus novemcinctus Linn.) as a model for the study of leprosy. I. Report of lepromatoid leprosy in an experimentally infected armadillo. Int J Lepr Other Mycobact Dis 39:693–702PubMedGoogle Scholar
  59. Klatser PR, van Beers S, Madjid B, Day R, de Wit MY (1993) Detection of Mycobacterium leprae nasal carriers in populations for which leprosy is endemic. J Clin Microbiol 31:2947–2951PubMedGoogle Scholar
  60. Klein J, Sato A (2000a) The HLA system. First of two parts. N Engl J Med 343:702–709PubMedGoogle Scholar
  61. Klein J, Sato A (2000b) The HLA system. Second of two parts. N Engl J Med 343:782–786PubMedGoogle Scholar
  62. Knight JC, Kwiatkowski D (1999) Inherited variability of tumor necrosis factor production and susceptibility to infectious disease. Proc Assoc Am Physicians 111:290–298PubMedGoogle Scholar
  63. Knight JC, Keating BJ, Kwiatkowski DP (2004) Allele-specific repression of lymphotoxin-[alpha] by activated B cell factor-1. Nat Genet 36:394–399PubMedGoogle Scholar
  64. Kocak M, Balci M, Pence B, Kundakci N (2002) Associations between human leukocyte antigens and leprosy in the Turkish population. Clin Exp Dermatol 27:235–239PubMedGoogle Scholar
  65. Kotb M, Norrby-Teglund A, McGeer A, El-Sherbini H, Dorak MT et al (2002) An immunogenetic and molecular basis for differences in outcomes of invasive group A streptococcal infections. Nat Med 8:1398–1404PubMedGoogle Scholar
  66. Krutzik SR, Ochoa MT, Sieling PA, Uematsu S, Ng YW et al (2003) Activation and regulation of Toll-like receptors 2 and 1 in human leprosy. Nat Med 9:525–532PubMedGoogle Scholar
  67. Krutzik SR, Tan B, Li H, Ochoa MT, Liu PT et al (2005) TLR activation triggers the rapid differentiation of monocytes into macrophages and dendritic cells. Nat Med 11:653–660PubMedGoogle Scholar
  68. Kulkarni S, Martin MP, Carrington M (2008) The Yin and Yang of HLA and KIR in human disease. Semin Immunol 20:343–352PubMedGoogle Scholar
  69. Lang HL, Jacobsen H, Ikemizu S, Andersson C, Harlos K et al (2002) A functional and structural basis for TCR cross-reactivity in multiple sclerosis. Nat Immunol 3:940–943PubMedGoogle Scholar
  70. Lazaro FP, Werneck RI, Mackert CC, Cobat A, Prevedello FC et al (2010) A major gene controls leprosy susceptibility in a hyperendemic isolated population from north of Brazil. J Infect Dis 201:1598–1605PubMedGoogle Scholar
  71. Lincoln MR, Montpetit A, Cader MZ, Saarela J, Dyment DA et al (2005) A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis. Nat Genet 37:1108–1112PubMedGoogle Scholar
  72. Lucking CB, Durr A, Bonifati V, Vaughan J, De Michele G et al (2000) Association between early-onset Parkinson’s disease and mutations in the parkin gene. N Engl J Med 342:1560–1567PubMedGoogle Scholar
  73. MacDonald KS, Fowke KR, Kimani J, Dunand VA, Nagelkerke NJ et al (2000) Influence of HLA supertypes on susceptibility and resistance to human immunodeficiency virus type 1 infection. J Infect Dis 181:1581–1589PubMedGoogle Scholar
  74. Malhotra D, Darvishi K, Lohra M, Kumar H, Grover C et al (2005a) 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 14:438–442Google Scholar
  75. Malhotra D, Relhan V, Reddy BS, Bamezai R (2005b) TLR2 Arg677Trp polymorphism in leprosy: revisited. Hum Genet 116:413–415PubMedGoogle Scholar
  76. Malo D, Vogan K, Vidal S, Hu J, Cellier M et al (1994) Haplotype mapping and sequence analysis of the mouse Nramp gene predict susceptibility to infection with intracellular parasites. Genomics 23:51–61PubMedGoogle Scholar
  77. McInturff JE, Modlin RL, Kim J (2005) The role of toll-like receptors in the pathogenesis and treatment of dermatological disease. J Invest Dermatol 125:1–8PubMedGoogle Scholar
  78. Mehra NK, Singh P, Sood P, Kaur G (2010) MHC and non-MHC genes in tuberculosis and leprosy. In: Mehra NK (ed) The HLA complex in biology and medicine: a resource book. Jaypee Bros. Medical Publishers, New Delhi, pp 386–405Google Scholar
  79. Meisner SJ, Mucklow S, Warner G, Sow SO, Lienhardt C et al (2001) Association of NRAMP1 polymorphism with leprosy type but not susceptibility to leprosy per se in west Africans. Am J Trop Med Hyg 65:733–735PubMedGoogle Scholar
  80. Meyer CG, May J, Stark K (1998) Human leukocyte antigens in tuberculosis and leprosy. Trends Microbiol 6:148–154PubMedGoogle Scholar
  81. Migita O, Noguchi E, Koga M, Jian Z, Shibasaki M et al (2005) Haplotype analysis of a 100 kb region spanning TNF-LTA identifies a polymorphism in the LTA promoter region that is associated with atopic asthma susceptibility in Japan. Clin Exp Allergy 35:790–796PubMedGoogle Scholar
  82. Miller EN, Jamieson SE, Joberty C, Fakiola M, Hudson D et al (2004) Genome-wide scans for leprosy and tuberculosis susceptibility genes in Brazilians. Genes Immun 5:63–67PubMedGoogle Scholar
  83. Mira MT (2006) Genetic host resistance and susceptibility to leprosy. Microbes Infect 8:1124–1131PubMedGoogle Scholar
  84. Mira MT, Alcais A, Van Thuc N, Thai VH, Huong NT et al (2003) Chromosome 6q25 is linked to susceptibility to leprosy in a Vietnamese population. Nat Genet 33:412–415PubMedGoogle Scholar
  85. Mira MT, Alcais A, Van Thuc N, Moraes MO, Di Flumeri C et al (2004) Susceptibility to leprosy is associated with PARK2 and PACRG. Nature 427:636–640PubMedGoogle Scholar
  86. Misch EA, Hawn TR (2008) Toll-like receptor polymorphisms and susceptibility to human disease. Clin Sci (Lond) 114:347–360Google Scholar
  87. Misch EA, Macdonald M, Ranjit C, Sapkota BR, Wells RD et al (2008) Human TLR1 deficiency is associated with impaired mycobacterial signaling and protection from leprosy reversal reaction. PLoS Negl Trop Dis 2:e231PubMedGoogle Scholar
  88. Mishina D, Katsel P, Brown ST, Gilberts EC, Greenstein RJ (1996) On the etiology of Crohn disease. Proc Natl Acad Sci USA 93:9816–9820PubMedGoogle Scholar
  89. Moegling A (1935) Die Epidemiologie der Lûbecker Säuglingstuberkulose. Arbeiten ad Reichsges-Amt 69:1–24Google Scholar
  90. Moffatt MF, Schou C, Faux JA, Abecasis GR, James A et al (2001) Association between quantitative traits underlying asthma and the HLA-DRB1 locus in a family-based population sample. Eur J Hum Genet 9:341–346PubMedGoogle Scholar
  91. Mohamed Ali P, Ramanujam K (1966) Leprosy in twins. Int J Lepr 34:405–407Google Scholar
  92. Nejentsev S, Howson JM, Walker NM, Szeszko J, Field SF et al (2007) Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A. Nature 450:887–892PubMedGoogle Scholar
  93. Nishi H, Koga Y, Koyanagi T, Harada H, Imaizumi T et al (1995) DNA typing of HLA class II genes in Japanese patients with dilated cardiomyopathy. J Mol Cell Cardiol 27:2385–2392PubMedGoogle Scholar
  94. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF et al (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 411:603–606PubMedGoogle Scholar
  95. Oksenberg JR, Barcellos LF, Cree BA, Baranzini SE, Bugawan TL et al (2004) Mapping multiple sclerosis susceptibility to the HLA-DR locus in African Americans. Am J Hum Genet 74:160–167PubMedGoogle Scholar
  96. Oliveira RB, Ochoa MT, Sieling PA, Rea TH, Rambukkana A et al (2003) Expression of Toll-like receptor 2 on human Schwann cells: a mechanism of nerve damage in leprosy. Infect Immun 71:1427–1433PubMedGoogle Scholar
  97. Orlova M, Schurr E (2010) Genetic architecture of mycobacterial diseases. In: Mehra NK (ed) The HLA complex in biology and medicine: a resource book. Jaypee Bros. Medical Publishers, New Delhi, pp 365–385Google Scholar
  98. Ozaki K, Ohnishi Y, Iida A, Sekine A, Yamada R et al (2002) Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction. Nat Genet 32:650–654PubMedGoogle Scholar
  99. Park BS, Park JS, Lee DY, Youn JI, Kim IG (1999) Vitamin D receptor polymorphism is associated with psoriasis. J Invest Dermatol 112:113–116PubMedGoogle Scholar
  100. Poon AH, Laprise C, Lemire M, Montpetit A, Sinnett D et al (2004) Association of vitamin D receptor genetic variants with susceptibility to asthma and atopy. Am J Respir Crit Care Med 170:967–973PubMedGoogle Scholar
  101. PROCARDIS Consortium (2004) A trio family study showing association of the lymphotoxin-alpha N26 (804A) allele with coronary artery disease. Eur J Hum Genet 12:770–774Google Scholar
  102. Raby BA, Lazarus R, Silverman EK, Lake S, Lange C et al (2004) Association of vitamin D receptor gene polymorphisms with childhood and adult asthma. Am J Respir Crit Care Med 170:1057–1065PubMedGoogle Scholar
  103. Rahman P, Bartlett S, Siannis F, Pellett FJ, Farewell VT et al (2003) CARD15: a pleiotropic autoimmune gene that confers susceptibility to psoriatic arthritis. Am J Hum Genet 73:677–681PubMedGoogle Scholar
  104. Reis AF, Hauache OM, Velho G (2005) Vitamin D endocrine system and the genetic susceptibility to diabetes, obesity and vascular disease. A review of evidence. Diabetes Metab 31:318–325PubMedGoogle Scholar
  105. Roach DR, Briscoe H, Saunders B, France MP, Riminton S et al (2001) Secreted lymphotoxin-{{alpha}} is essential for the control of an intracellular bacterial infection. J Exp Med 193:239–246PubMedGoogle Scholar
  106. Roach D, Briscoe H, Saunders B, Britton W (2005) Independent protective effects for tumor necrosis factor and lymphotoxin alpha in the host response to Listeria monocytogenes infection. Infect Immun 73:4787–4792PubMedGoogle Scholar
  107. Saadi A, Gao G, Li H, Wei C, Gong Y et al (2009) Association study between vitamin D receptor gene polymorphisms and asthma in the Chinese Han population: a case-control study. BMC Med Genet 10:71PubMedGoogle Scholar
  108. Saeki H, Asano N, Tsunemi Y, Takekoshi T, Kishimoto M et al (2002) Polymorphisms of vitamin D receptor gene in Japanese patients with psoriasis vulgaris. J Dermatol Sci 30:167–171PubMedGoogle Scholar
  109. Schurr E, Gros P (2009) A common genetic fingerprint in leprosy and Crohn’s disease? N Engl J Med 361:2666–2668PubMedGoogle Scholar
  110. Scollard DM, Joyce MP, Gillis TP (2006) Development of leprosy and type 1 leprosy reactions after treatment with infliximab: a report of 2 cases. Clin Infect Dis 43:e19–e22PubMedGoogle Scholar
  111. Shankarkumar U (2004) HLA associations in leprosy patients from Mumbai, India. Lepr Rev 75:79–85PubMedGoogle Scholar
  112. Sharma S, Sharma A, Kumar S, Sharma SK, Ghosh B (2006) Association of TNF haplotypes with asthma, serum IgE levels, and correlation with serum TNF-alpha levels. Am J Respir Cell Mol Biol 35:488–495PubMedGoogle Scholar
  113. Shaw MA, Donaldson IJ, Collins A, Peacock CS, Lins-Lainson Z et al (2001) Association and linkage of leprosy phenotypes with HLA class II and tumour necrosis factor genes. Genes Immun 2:196–204PubMedGoogle Scholar
  114. Shaw MH, Reimer T, Kim YG, Nunez G (2008) NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Curr Opin Immunol 20:377–382PubMedGoogle Scholar
  115. Shepard CC (1960) The experimental disease that follows the injection of human leprosy bacilli into footpads of mice. J Exp Med 112:445–454PubMedGoogle Scholar
  116. Shields ED, Russell DA, Pericak-Vance MA (1987) Genetic epidemiology of the susceptibility to leprosy. J Clin Invest 79:1139–1143PubMedGoogle Scholar
  117. Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S et al (2000) Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet 25:302–305PubMedGoogle Scholar
  118. Shin HD, Yang SW, Kim DH, Park Y (2008) Independent association of tumor necrosis factor polymorphism with type 1 diabetes susceptibility. Ann NY Acad Sci 1150:76–85PubMedGoogle Scholar
  119. Siddiqui MR, Meisner S, Tosh K, Balakrishnan K, Ghei S et al (2001) A major susceptibility locus for leprosy in India maps to chromosome 10p13. Nat Genet 27:439–441PubMedGoogle Scholar
  120. Smith DG (1979) The genetic hypothesis for susceptibility to lepromatous leprosy. Hum Genet 50:163–177PubMedGoogle Scholar
  121. Smith WW, Pei Z, Jiang H, Moore DJ, Liang Y et al (2005) Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. Proc Natl Acad Sci USA 102:18676–18681PubMedGoogle Scholar
  122. Sorensen TI, Nielsen GG, Andersen PK, Teasdale TW (1988) Genetic and environmental influences on premature death in adult adoptees. N Engl J Med 318:727–732PubMedGoogle Scholar
  123. Thursz M, Yallop R, Goldin R, Trepo C, Thomas HC (1999) Influence of MHC class II genotype on outcome of infection with hepatitis C virus. The HENCORE group. Hepatitis C European Network for Cooperative Research. Lancet 354:2119–2124PubMedGoogle Scholar
  124. Tobin DM, Vary JC Jr, Ray JP, Walsh GS, Dunstan SJ et al (2010) The lta4 h locus modulates susceptibility to mycobacterial infection in zebrafish and humans. Cell 140:717–730PubMedGoogle Scholar
  125. Via M, De Giacomo A, Corvol H, Eng C, Seibold MA et al (2010) The role of LTA4H and ALOX5AP genes in the risk for asthma in Latinos. Clin Exp Allergy 40:582–589PubMedGoogle Scholar
  126. Vidal SM, Pinner E, Lepage P, Gauthier S, Gros P (1996) Natural resistance to intracellular infections: Nramp1 encodes a membrane phosphoglycoprotein absent in macrophages from susceptible (Nramp1 D169) mouse strains. J Immunol 157:3559–3568PubMedGoogle Scholar
  127. Vyakarnam A, Sidebottom D, Murad S, Underhill JA, Easterbrook PJ et al (2004) Possession of human leucocyte antigen DQ6 alleles and the rate of CD4 T-cell decline in human immunodeficiency virus-1 infection. Immunology 112:136–142PubMedGoogle Scholar
  128. Wagener DK, Schauf V, Nelson KE, Scollard D, Brown A et al (1988) Segregation analysis of leprosy in families of northern Thailand. Genet Epidemiol 5:95–105PubMedGoogle Scholar
  129. Wang LM, Kimura A, Satoh M, Mineshita S (1999) HLA linked with leprosy in southern China: HLA-linked resistance alleles to leprosy. Int J Lepr Other Mycobact Dis 67:403–408PubMedGoogle Scholar
  130. Weidinger S, Klopp N, Rummler L, Wagenpfeil S, Baurecht HJ et al (2005) Association of CARD15 polymorphisms with atopy-related traits in a population-based cohort of Caucasian adults. Clin Exp Allergy 35:866–872PubMedGoogle Scholar
  131. Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661–678Google Scholar
  132. Wheeler E, Miller EN, Peacock CS, Donaldson IJ, Shaw MA et al (2006) Genome-wide scan for loci influencing quantitative immune response traits in the Belem family study: comparison of methods and summary of results. Ann Hum Genet 70:78–97PubMedGoogle Scholar
  133. WHO (2008) Global leprosy situation, beginning of 2008. Wkly Epidemiol Rec 83:293–300Google Scholar
  134. Wong SH, Hill AV, Vannberg FO (2010) Genomewide association study of leprosy. N Engl J Med 362:1446–1447 (author reply 1447–1448)PubMedGoogle Scholar
  135. Yang SK, Lee SG, Cho YK, Lim J, Lee I et al (2006) Association of TNF-alpha/LTA polymorphisms with Crohn’s disease in Koreans. Cytokine 35:13–20PubMedGoogle Scholar
  136. Yee LJ, Thursz MR (2004) Genetic diversity in the major histocompatibility complex and the immune response to infectious diseases. In: Bellamy R (ed) Susceptibility to infectious diseases: the importance of host genetics (advances in molecular and cellular microbiology). Cambridge University Press, CambridgeGoogle Scholar
  137. Zerva L, Cizman B, Mehra NK, Alahari SK, Murali R et al (1996) Arginine at positions 13 or 70–71 in pocket 4 of HLA-DRB1 alleles is associated with susceptibility to tuberculoid leprosy. J Exp Med 183:829–836PubMedGoogle Scholar
  138. Zhang FR, Huang W, Chen SM, Sun LD, Liu H et al (2009) Genomewide association study of leprosy. N Engl J Med 361:2609–2618PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Andrea Alter
    • 1
    • 2
  • Audrey Grant
    • 3
    • 4
  • Laurent Abel
    • 3
    • 4
    • 5
  • Alexandre Alcaïs
    • 3
    • 4
    • 5
  • Erwin Schurr
    • 1
    • 2
    • 6
  1. 1.Research Institute of the McGill University Health Centre, McGill Centre for the Study of Host Resistance, Department of MedicineMcGill UniversityMontrealCanada
  2. 2.Research Institute of the McGill University Health Centre, McGill Centre for the Study of Host Resistance, Department of Human GeneticsMcGill UniversityMontrealCanada
  3. 3.Laboratoire de Génétique des Maladies Infectieuses, Institut National de la Santé et de la Recherche Médicale, U550ParisFrance
  4. 4.Faculté Médicine NeckerUniversité Paris René DescartesParisFrance
  5. 5.St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller BranchThe Rockefeller UniversityNew YorkUSA
  6. 6.Montreal General Hospital Research InstituteMontrealCanada

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