Susceptibility to leprosy is associated with PARK2 and PACRG

Susceptibility to leprosy is associated with PARK2 and PACRG Mira M.T., Alcais A., Van Thuc H., Moraes M.O., Di Flumeri C., Thai V.I., Phuong M.C., Huong N.T., Ba N.N., Khoa P.X., Sarno E.N., Alter A., Monipetit A., Moraes M.E., Moraes J.R., Dore C., Gallant C.J., Lepage P., Verner A., Van De Vosse E., Hudson T.J., Abel L., Schurr E McGill Ctr Stud Host Resist., Depts of Hum Genet., Med./Biochem., McGill University, 1650 Cedar Avenue, Montreal, Que H3G1A4, Canada; Ctro de Cie Biologicas e da Saude, Pont Univ Catolica Parana, Rua Imaculada Conceicao, 1155, CEP 80215-901, Curitiba, Parana, Brazil; INSERM U.550, Faculte de Medecine Necker, Universite de Paris Rene Descartes, 156 rue de Vaugirard, 75015 Paris, France; Hospital for Dermato-Venereology, Nguyen Thong Street, District 3, Ho Chi Minh City, Viet Nam; Leprosy Laboratory, Tropical Medicine Department, Oswaldo Cruz Institute, FIOCRUZ 20221-903 Rio de Janeiro, Brazil; McGill University, Genome Quebec Innovation Centre, 740 Docteur Penfield, Montreal, Que H3A 1A4, Canada; Laboratorio de Imunogenetica, Instituto Nacional Cancer, Ministério da Saúde, 20230-130 Rio de Janeiro, RJ, Brazil; Department of Infectious Diseases, Leiden University Medical Center, Building 1, Albinusdreef 2, 2333 ZA Leiden, Netherlands 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 component2, and recently we mapped a leprosy susceptibility locus to chromosome 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 Index Keywords: Bacteria; Genes; Genetic engineering; Alleles; Leprosy; Diseases; leprosy; allele; article; bacterial gene; chromosome 6q; controlled study; family study; gene expression; gene linkage disequilibrium; gene mapping; genetic marker; genetic susceptibility; genetic variability; genotype; human; infection sensitivity; leprosy; major clinical study; Mycobacterium leprae; PACRG gene; park2 gene; phenotype; priority journal; regulator gene; risk factor; single nucleotide polymorphism; Viet Nam; Alleles; Brazil; Case-Control Studies; Chromosome Mapping; Chromosomes, Human, Pair 6; Gene Expression Profiling; Genetic Predisposition to Disease; Haplotypes; Humans; Leprosy; Molecular Chaperones; Phenotype; Polymorphism, Single Nucleotide; Proteins; RNA, Messenger; Ubiquitin-Protein Ligases; Vietnam; Bacteria (microorganisms); Mycobacterium leprae; Posibacteria Year: 2004 Source title: Nature Volume: 427 Issue: 6975 Page : 636-640 Cited by: 148 Link: Scorpus Link Correspondence Address: Abel, L.; INSERM U.550, Faculte de Medecine Necker, Universite de Paris Rene Descartes, 156 rue de Vaugirard, 75015 Paris, France; email: abel@necker.fr Document Type: Article Source: Scopus Authors with affiliations: Mira, M.T., McGill Ctr Stud Host Resist., Depts of Hum Genet., Med./Biochem., McGill University, 1650 Cedar Avenue, Montreal, Que H3G1A4, Canada, Ctro de Cie Biologicas e da Saude, Pont Univ Catolica Parana, Rua Imaculada Conceicao, 1155, CEP 80215-901, Curitiba, Parana, Brazil Alcaïs, A., INSERM U.550, Faculte de Medecine Necker, Universite de Paris Rene Descartes, 156 rue de Vaugirard, 75015 Paris, France Van Thuc, H., Hospital for Dermato-Venereology, Nguyen Thong Street, District 3, Ho Chi Minh City, Viet Nam Moraes, M.O., Leprosy Laboratory, Tropical Medicine Department, Oswaldo Cruz Institute, FIOCRUZ 20221-903 Rio de Janeiro, Brazil Di Flumeri, C., McGill Ctr Stud Host Resist., Depts of Hum Genet., Med./Biochem., McGill University, 1650 Cedar Avenue, Montreal, Que H3G1A4, Canada Thai, V.I., Hospital for Dermato-Venereology, Nguyen Thong Street, District 3, Ho Chi Minh City, Viet Nam Phuong, M.C., Hospital for Dermato-Venereology, Nguyen Thong Street, District 3, Ho Chi Minh City, Viet Nam Huong, N.T., Hospital for Dermato-Venereology, Nguyen Thong Street, District 3, Ho Chi Minh City, Viet Nam Ba, N.N., Hospital for Dermato-Venereology, Nguyen Thong Street, District 3, Ho Chi Minh City, Viet Nam 10 Khoa, P.X., Hospital for Dermato-Venereology, Nguyen Thong Street, District 3, Ho Chi Minh City, Viet Nam 11 Sarno, E.N., Leprosy Laboratory, Tropical Medicine Department, Oswaldo Cruz Institute, FIOCRUZ 20221-903 Rio de Janeiro, Brazil 12 Alter, A., McGill Ctr Stud Host Resist., Depts of Hum Genet., Med./Biochem., McGill University, 1650 Cedar Avenue, Montreal, Que H3G1A4, Canada 13 Monipetit, A., McGill University, Genome Quebec Innovation Centre, 740 Docteur Penfield, Montreal, Que H3A 1A4, Canada 14 Moraes, M.E., Laboratorio de Imunogenetica, Instituto Nacional Cancer, Ministério da Saúde, 20230-130 Rio de Janeiro, RJ, Brazil 15 Moraes, J.R., Laboratorio de Imunogenetica, Instituto Nacional Cancer, Ministério da Saúde, 20230-130 Rio de Janeiro, RJ, Brazil 16 Doré, C., McGill University, Genome Quebec Innovation Centre, 740 Docteur Penfield, Montreal, Que H3A 1A4, Canada 17 Gallant, C.J., McGill Ctr Stud Host Resist., Depts of Hum Genet., Med./Biochem., McGill University, 1650 Cedar Avenue, Montreal, Que H3G1A4, Canada 18 Lepage, P., McGill University, Genome Quebec Innovation Centre, 740 Docteur Penfield, Montreal, Que H3A 1A4, Canada 19 Verner, A., McGill University, Genome Quebec Innovation Centre, 740 Docteur Penfield, Montreal, Que H3A 1A4, Canada 20 Van De Vosse, E., Department of Infectious Diseases, Leiden University Medical Center, Building 1, Albinusdreef 2, 2333 ZA Leiden, Netherlands 21 Hudson, T.J., McGill Ctr Stud Host Resist., Depts of Hum Genet., Med./Biochem., McGill University, 1650 Cedar Avenue, Montreal, Que H3G1A4, Canada, McGill University, Genome Quebec Innovation Centre, 740 Docteur Penfield, Montreal, Que H3A 1A4, Canada 22 Abel, L., INSERM U.550, Faculte de Medecine Necker, Universite de Paris Rene Descartes, 156 rue de Vaugirard, 75015 Paris, France 23 Schurr, E., McGill Ctr Stud Host Resist., Depts of Hum Genet., Med./Biochem., McGill University, 1650 Cedar Avenue, Montreal, Que H3G1A4, Canada References: Leprosy Global situation (2002) Wkly Epidemiol Rec., 77, pp 1-8 Casanova, J.L., Abel, L., Genetic dissection of immunity to mycobacteria: The human model (2002) Annu Rev Immunol., 20, pp 581-620 Mira, M.T., Chromosome 6q25 is linked to susceptibility to leprosy in a 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Laboratorio de Imunogenetica, Instituto Nacional Cancer, Ministério da Saúde, 20230-130 Rio de Janeiro, RJ, Brazil 15 Moraes, J.R., Laboratorio de Imunogenetica, Instituto Nacional Cancer, Ministério... de Vaugirard, 75015 Paris, France Van Thuc, H., Hospital for Dermato-Venereology, Nguyen Thong Street, District 3, Ho Chi Minh City, Viet Nam Moraes, M.O., Leprosy Laboratory, Tropical Medicine