Mapping of a novel susceptibility locus suggests a role for MC3R and CTSZ in human tuberculosis.

American Journal of Respiratory and Critical Care Medicine
Graham S CookeAdrian V S Hill

Abstract

Tuberculosis remains a major cause of morbidity and mortality in the developing world. A better understanding of the mechanisms of disease protection could allow novel strategies to disease management and control. To identify human genomic loci with evidence of linkage to tuberculosis susceptibility and, within these loci, to identify individual genes influencing tuberculosis susceptibility. Affected sibling pair analysis in South African and Malawian populations. Independent case-control study in West Africa. Two novel putative loci for tuberculosis susceptibility are identified: chromosome 6p21-q23 and chromosome 20q13.31-33--the latter with the strongest evidence for any locus reported to date in human tuberculosis (single point LOD score of 3.1, P = 10(-4), with a maximum likelihood score [MLS] of 2.8). An independent, multistage genetic association study in West African populations mapped this latter region in detail, finding evidence that variation in the melanocortin 3 receptor (MC3R) and cathepsin Z (CTSZ) genes play a role in the pathogenesis of tuberculosis. These results demonstrate how a genomewide approach to the complex phenotype of human tuberculosis can identify novel targets for further research.

References

Jun 1, 1991·Tubercle·V BrahmajothiR Prabhakar
Mar 5, 1998·The New England Journal of Medicine·R BellamyA V Hill
Jun 23, 1998·American Journal of Human Genetics·J R O'Connell, D E Weeks
Jun 27, 1998·The Journal of Biological Chemistry·I SantamaríaC López-Otín
Feb 10, 2000·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·S J GettingM Perretti
Mar 9, 2000·Tubercle and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease·M RavikumarR M Pitchappan
Jun 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·R BellamyA V Hill
Jan 10, 2001·The Journal of Cell Biology·J GarinM Desjardins
Mar 30, 2001·Nature Genetics·M R SiddiquiA V Hill
Apr 21, 2001·Cellular and Molecular Life Sciences : CMLS·Z A Abdel-Malek
Dec 4, 2001·Nature Genetics·Gonçalo R AbecasisLon R Cardon
Jun 21, 2002·Human Molecular Genetics·Alessandra C L CervinoAdrian V S Hill
Aug 21, 2002·The Journal of Experimental Medicine·Ana-Maria Lennon-DuménilCécile Lagaudrière-Gesbert
Oct 2, 2002·The Journal of Infectious Diseases·Kerrie ToshAdrian V S Hill
Oct 3, 2002·European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics·D LioC Caruso
Oct 31, 2002·The Journal of Infectious Diseases·Julio C DelgadoAnne E Goldfeld
Nov 26, 2002·The Journal of Infectious Diseases·Agnes A AwomoyiMelanie J Newport
Jan 18, 2003·American Journal of Respiratory and Critical Care Medicine·Dolores López-MaderueloCarmen Montiel
Feb 11, 2003·Nature Genetics·Marcelo T MiraErwin Schurr
May 17, 2003·The Journal of Pharmacology and Experimental Therapeutics·Stephen J GettingMauro Perretti
Jan 22, 2004·Genes and Immunity·E N MillerJ M Blackwell
Jan 23, 2004·Nature·Marcelo T MiraErwin Schurr
May 13, 2006·American Journal of Respiratory and Critical Care Medicine·Graham S CookeAdrian V S Hill
Nov 2, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Stephen J GettingMauro Perretti
Aug 13, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hetal B PatelMauro Perretti

❮ Previous
Next ❯

Citations

Mar 4, 2011·European Journal of Human Genetics : EJHG·Lindsey A AdamsEileen G Hoal
Dec 16, 2011·Genes and Immunity·N T T ThuongS J Dunstan
Dec 24, 2010·Journal of Human Genetics·Hui-Qi QuJoseph B McCormick
May 4, 2012·Journal of Human Genetics·Surakameth MahasirimongkolKatsushi Tokunaga
Oct 1, 2008·Nature Reviews. Genetics·Billie-Jo HardyAbdallah S Daar
Jan 10, 2012·The Journal of Infectious Diseases·Robert John Wilkinson
Feb 9, 2012·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Adrian V S Hill
Jul 25, 2012·Infection and Immunity·Abul K AzadLarry S Schlesinger
Feb 24, 2009·American Journal of Respiratory and Critical Care Medicine·Wing Wai Yew, Chi Chiu Leung
Jan 1, 2009·PloS One·Catherine M SteinChristopher C Whalen
Dec 6, 2008·PLoS Pathogens·Nguyen Thuy Thuong ThuongThomas R Hawn
Sep 18, 2014·Journal of Molecular Endocrinology·Hui Huang, Ya-Xiong Tao
Aug 16, 2011·Der Internist·S J Ott, S Schreiber
Mar 16, 2012·Scandinavian Journal of Immunology·T QidwaiM Y Khan
Mar 24, 2016·Genetic Testing and Molecular Biomarkers·Yun XueFan Chen
Sep 29, 2009·FEMS Immunology and Medical Microbiology·Marlo MöllerEileen G Hoal
Jul 14, 2017·Expert Review of Respiratory Medicine·Craig KinnearMarlo Möller
Oct 18, 2019·Frontiers in Genetics·Wilian Correa-MacedoErwin Schurr
Feb 24, 2017·Molecular Genetics and Genomics : MGG·Caitlin UrenEileen G Hoal
Aug 18, 2018·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Monica Dallmann-SauerErwin Schurr
Nov 30, 2018·Frontiers in Immunology·Elouise E KroonErwin Schurr
Oct 28, 2016·Microbiology Spectrum·Vivek Naranbhai

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antitubercular Agents (ASM)

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Antitubercular Agents

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

American Thoracic Association Journals

Discover the latest respiratory research published by the journals from the American Thoracic Society.