Susceptibility to leprosy is associated with PARK2 and PACRG

• Published in: Nature Vol. 427; no. 6975; pp. 636 - 640
• Main Authors: Abel, Laurent, Schurr, Erwin, Mira, Marcelo T, Alcaïs, Alexandre, Van Thuc, Nguyen, Moraes, Milton O, Di Flumeri, Celestino, Hong Thai, Vu, Chi Phuong, Mai, Thu Huong, Nguyen, Ngoc Ba, Nguyen, Xuan Khoa, Pham, Sarno, Euzenir N, Alter, Andrea, Montpetit, Alexandre, Moraes, Maria E, Moraes, José R, Doré, Carole, Gallant, Caroline J, Lepage, Pierre, Verner, Andrei, van de Vosse, Esther, Hudson, Thomas J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 12-02-2004; Nature Publishing Group
• Subjects: Alleles; Biological and medical sciences; Brazil; Case-Control Studies; chromosome 6; Chromosome Mapping; Chromosomes, Human, Pair 6 - genetics; Families & family life; Gene Expression Profiling; General aspects; Genetic Predisposition to Disease; Genetics; Haplotypes; Human infectious diseases. Experimental studies and models; Humans; Infectious diseases; Leprosy; Leprosy - genetics; Medical sciences; Molecular Chaperones; Mycobacterium leprae; PACRG gene; PARK2 gene; Parkinson's disease; Phenotype; Polymorphism, Single Nucleotide - genetics; Proteins - genetics; Risk factors; RNA, Messenger - analysis; RNA, Messenger - genetics; Studies; Ubiquitin-Protein Ligases - genetics; Vietnam; Vietnam; Infection; Human; Skin disease; Gene; Predisposition; Bacteriosis; Leprosy; Mycobacterial infection
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature02326

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.