title: MARCO variants are associated with phagocytosis, pulmonary tuberculosis susceptibility and Beijing lineage.
abstract: Macrophage receptor with collagenous structure (MARCO) has an important role in the phagocytosis of Mycobacterium tuberculosis (M. tuberculosis). We hypothesized that MARCO polymorphisms are associated with phagocytosis, tuberculosis (TB) disease susceptibility and presentation, and infecting lineage. We used a human cellular model to examine how MARCO genotype mediates the immune response; a case-control study to investigate tuberculosis host genetic susceptibility; and a host-pathogen genetic analysis to study host-pathogen interactions. Two MARCO heterozygous (AG) genotypes (single-nucleotide polymorphisms rs2278589 and rs6751745) were associated with impaired phagocytosis of M. tuberculosis trehalose 6,6'-dimycolate-cord factor and β-glucan-coated beads in macrophages. The heterozygous genotypes of rs2278589 and rs6751745 were also associated with increased risk of pulmonary TB (PTB; rs2278589, P=0.001, odds ratio (OR)=1.6; rs6751745, P=0.009, OR=1.4), and with severe chest X-ray abnormalities (P=0.007, OR=1.6). These two genotypes were also associated with the Beijing lineage (rs2278589, P=0.001, OR=1.7; rs6751745, P=0.01, OR=1.5). Together, these results suggest that MARCO polymorphisms may regulate phagocytosis of M. tuberculosis and susceptibility and severity of PTB. They also suggest MARCO genotype and Beijing strains may interact to increase the risk of PTB.
authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: N T T
authors.initials: NT
authors.lastname: Thuong
authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: T T B
authors.initials: TT
authors.lastname: Tram
authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: T D
authors.initials: TD
authors.lastname: Dinh
authors.affiliation: Pham Ngoc Thach Hospital for Tuberculosis and Lung Disease, Ho Chi Minh City, Vietnam.
authors.forename: P V K
authors.initials: PV
authors.lastname: Thai
authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: D
authors.initials: D
authors.lastname: Heemskerk
authors.affiliation: Pham Ngoc Thach Hospital for Tuberculosis and Lung Disease, Ho Chi Minh City, Vietnam.
authors.forename: N D
authors.initials: ND
authors.lastname: Bang
authors.affiliation: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: T T H
authors.initials: TT
authors.lastname: Chau
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
authors.forename: D G
authors.initials: DG
authors.lastname: Russell
authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: G E
authors.initials: GE
authors.lastname: Thwaites
authors.affiliation: Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Hawn
authors.affiliation: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK.
authors.forename: M
authors.initials: M
authors.lastname: Caws
authors.affiliation: Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
authors.forename: S J
authors.initials: SJ
authors.lastname: Dunstan
mesh_terms: D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000276:immunology*; D010587:Phagocytosis; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000235:genetics*; D014390:Tuberculosis, Meningeal / Q000235:genetics / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000382:microbiology
chemical_list: D016207:Cytokines; C490460:MARCO protein, human; D012333:RNA, Messenger; D011971:Receptors, Immunologic