Susceptibility to leprosy is associated with PARK2 and PACRG.
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.
Mira
Marcelo T
MT
McGill Centre for the Study of Host Resistance and Department of Human Genetics, McGill University, 1650 Cedar Avenue, Montreal, PQ H3G1A4, Canada.
Alcaïs
Alexandre
A
Nguyen
Van Thuc
VT
Moraes
Milton O
MO
Di Flumeri
Celestino
C
Vu
Hong Thai
HT
Mai
Chi Phuong
CP
Nguyen
Thu Huong
TH
Nguyen
Ngoc Ba
NB
Pham
Xuan Khoa
XK
Sarno
Euzenir N
EN
Alter
Andrea
A
Montpetit
Alexandre
A
Moraes
Maria E
ME
Moraes
José R
JR
Doré
Carole
C
Gallant
Caroline J
CJ
Lepage
Pierre
P
Verner
Andrei
A
Van De Vosse
Esther
E
Hudson
Thomas J
TJ
Abel
Laurent
L
Schurr
Erwin
E
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
D008840:Microfilament Proteins; D018832:Molecular Chaperones; C471711:PACRG protein, human; D011506:Proteins; D012333:RNA, Messenger; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein