MARCO variants are associated with phagocytosis, pulmonary tuberculosis susceptibility and Beijing lineage

Thuong, NT, Tram, TT, Dinh, TD, Thai, PV, Heemskerk, D, Bang, ND, Chau, TT, Russell, DG, Thwaites, GE, Hawn, TR, Caws, Maxine ORCID: https://orcid.org/0000-0002-9109-350X and Dunstan, SJ (2016) 'MARCO variants are associated with phagocytosis, pulmonary tuberculosis susceptibility and Beijing lineage'. Genes and Immunity, Vol 17, pp. 419-425.

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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

Item Type:	Article
Subjects:	QW Microbiology and Immunology > Bacteria > QW 125 Actinibacteria, Actinomycetales. WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General) WH Hemic and Lymphatic Systems > Lymphatic System > WH 650 Reticuloendothelial system
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1038/gene.2016.43
Depositing User:	Julie Franco
Date Deposited:	29 Nov 2016 11:06
Last Modified:	06 Feb 2018 13:13
URI:	https://archive.lstmed.ac.uk/id/eprint/6400

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