title: Susceptibility to leprosy is associated with PARK2 and PACRG.
abstract: Leprosy is caused by Mycobacterium leprae and affects about 700,000 individuals each year. It has long been thought that leprosy has a strong genetic component, 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.
authors.affiliation: McGill Centre for the Study of Host Resistance and Department of Human Genetics, McGill University, 1650 Cedar Avenue, Montreal, PQ H3G1A4, Canada.
authors.forename: Marcelo T
authors.initials: MT
authors.lastname: Mira
authors.forename: Alexandre
authors.initials: A
authors.lastname: Alcaïs
authors.forename: Van Thuc
authors.initials: VT
authors.lastname: Nguyen
authors.forename: Milton O
authors.initials: MO
authors.lastname: Moraes
authors.forename: Celestino
authors.initials: C
authors.lastname: Di Flumeri
authors.forename: Hong Thai
authors.initials: HT
authors.lastname: Vu
authors.forename: Chi Phuong
authors.initials: CP
authors.lastname: Mai
authors.forename: Thu Huong
authors.initials: TH
authors.lastname: Nguyen
authors.forename: Ngoc Ba
authors.initials: NB
authors.lastname: Nguyen
authors.forename: Xuan Khoa
authors.initials: XK
authors.lastname: Pham
authors.forename: Euzenir N
authors.initials: EN
authors.lastname: Sarno
authors.forename: Andrea
authors.initials: A
authors.lastname: Alter
authors.forename: Alexandre
authors.initials: A
authors.lastname: Montpetit
authors.forename: Maria E
authors.initials: ME
authors.lastname: Moraes
authors.forename: José R
authors.initials: JR
authors.lastname: Moraes
authors.forename: Carole
authors.initials: C
authors.lastname: Doré
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Gallant
authors.forename: Pierre
authors.initials: P
authors.lastname: Lepage
authors.forename: Andrei
authors.initials: A
authors.lastname: Verner
authors.forename: Esther
authors.initials: E
authors.lastname: Van De Vosse
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Erwin
authors.initials: E
authors.lastname: Schurr
mesh_terms: D000483:Alleles; D001938:Brazil; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007918:Leprosy / Q000235:genetics*; D008840:Microfilament Proteins; D018832:Molecular Chaperones; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D014744:Vietnam
chemical_list: D008840:Microfilament Proteins; D018832:Molecular Chaperones; C471711:PACRG protein, human; D011506:Proteins; D012333:RNA, Messenger; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein