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Nature 427, 636-640 (12 February 2004) | doi:10.1038/nature02326; Received 16 September 2003; Accepted 7 January 2004; Published online 25 January 2004

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Susceptibility to leprosy is associated with PARK2 and PACRG

Marcelo T. Mira1,2,9, Alexandre Alcaïs3,9, Nguyen Van Thuc4, Milton O. Moraes5, Celestino Di Flumeri1, Vu Hong Thai4, Mai Chi Phuong4, Nguyen Thu Huong4, Nguyen Ngoc Ba4, Pham Xuan Khoa4, Euzenir N. Sarno5, Andrea Alter1, Alexandre Montpetit6, Maria E. Moraes7, José R. Moraes7, Carole Doré6, Caroline J. Gallant1, Pierre Lepage6, Andrei Verner6, Esther van de Vosse8, Thomas J. Hudson1,6, Laurent Abel3 & Erwin Schurr1

  1. McGill Centre for the Study of Host Resistance and Departments of Human Genetics, Medicine and Biochemistry, McGill University, 1650 Cedar Avenue, Montreal, PQ H3G1A4, Canada
  2. Centro de Ciências Biológicas e da Saúde, Pontifícia Universidade Católica do Paraná. Rua Imaculada Conceição, 1155, CEP 80215-901, Curitiba, Paraná, Brasil
  3. Laboratoire de Génétique Humaine des Maladies Infectieuses, INSERM U.550, Faculté de Médecine Necker, Université de Paris René Descartes, 156 rue de Vaugirard, 75015 Paris, France
  4. Hospital for Dermato-Venereology, Nguyen Thong Street, District 3, Ho Chi Minh City, Vietnam
  5. Leprosy Laboratory, Tropical Medicine Department Oswaldo Cruz Institute, FIOCRUZ 20221-903 Rio de Janeiro, Brazil
  6. McGill University and Genome Québec Innovation Centre, 740 Docteur Penfield, Montreal, PQ H3A 1A4, Canada
  7. Laboratório de Imunogénetica, Instituto Nacional do Cancer, Ministério da Saúde, 20230-130 Rio de Janeiro, RJ, Brazil
  8. Department of Infectious Diseases & Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Building 1, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
  9. These authors contributed equally to this work

Correspondence to: Laurent Abel3Erwin Schurr1 Email: abel@necker.fr
Email: erwin@igloo.epi.mcgill.ca

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Leprosy is caused by Mycobacterium leprae and affects about 700,000 individuals each year1. It has long been thought that leprosy has a strong genetic component2, and recently we mapped a leprosy susceptibility locus to chromosome 6 region q25–q26 (ref. 3). Here we investigate this region further by using a systematic association scan of the chromosomal interval most likely to harbour this leprosy susceptibility locus. In 197 Vietnamese families we found a significant association between leprosy and 17 markers located in a block of approx. 80 kilobases overlapping the 5' regulatory region shared by the Parkinson's disease gene PARK2 and the co-regulated gene PACRG. Possession of as few as two of the 17 risk alleles was highly predictive of leprosy. This was confirmed in a sample of 975 unrelated leprosy cases and controls from Brazil in whom the same alleles were strongly associated with leprosy. Variants in the regulatory region shared by PARK2 and PACRG therefore act as common risk factors for leprosy.