Susceptibility to leprosy is associated with PARK2 and PACRG

Marcelo T. Mira, Alexandre Alcaïs, Nguyen Van Thuc, Milton O. Moraes, Celestino Di Flumeri, Vu Hong Thai, Mai Chi Phuong, Nguyen Thu Huong, Nguyen Ngoc Ba, Pham Xuan Khoa, Euzenir N. Sarno, Andrea Alter, Alexandre Montpetit, Maria E. Moraes, José R. Moraes, Carole Doré, Caroline J. Gallant, Pierre Lepage, Andrei Verner, Esther van de Vosse, Thomas J. Hudson, Laurent Abel () and Erwin Schurr ()
Additional contact information
Marcelo T. Mira: McGill University
Alexandre Alcaïs: Université de Paris René Descartes
Nguyen Van Thuc: Hospital for Dermato-Venereology
Milton O. Moraes: Leprosy Laboratory, Tropical Medicine Department Oswaldo Cruz Institute, FIOCRUZ
Celestino Di Flumeri: McGill University
Vu Hong Thai: Hospital for Dermato-Venereology
Mai Chi Phuong: Hospital for Dermato-Venereology
Nguyen Thu Huong: Hospital for Dermato-Venereology
Nguyen Ngoc Ba: Hospital for Dermato-Venereology
Pham Xuan Khoa: Hospital for Dermato-Venereology
Euzenir N. Sarno: Leprosy Laboratory, Tropical Medicine Department Oswaldo Cruz Institute, FIOCRUZ
Andrea Alter: McGill University
Alexandre Montpetit: McGill University and Genome Québec Innovation Centre
Maria E. Moraes: Instituto Nacional do Cancer, Ministério da Saúde
José R. Moraes: Instituto Nacional do Cancer, Ministério da Saúde
Carole Doré: McGill University and Genome Québec Innovation Centre
Caroline J. Gallant: McGill University
Pierre Lepage: McGill University and Genome Québec Innovation Centre
Andrei Verner: McGill University and Genome Québec Innovation Centre
Esther van de Vosse: Leiden University Medical Center
Thomas J. Hudson: McGill University
Laurent Abel: Université de Paris René Descartes
Erwin Schurr: McGill University

Nature, 2004, vol. 427, issue 6975, 636-640

Abstract: Abstract 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.

Date: 2004
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DOI: 10.1038/nature02326

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