title: Genetic variants of MARCO are associated with susceptibility to pulmonary tuberculosis in a Gambian population.
abstract: BACKGROUND
  The two major class A scavenger receptors are scavenger receptor A (SRA), which is constitutively expressed on most macrophage populations, and macrophage receptor with collagenous structure (MARCO), which is constitutively expressed on a more restricted subset of macrophages, (e.g. alveolar macrophages) but whose expression increases on most macrophages during the course of infection. Although the primary role of SRA appears to be clearance of modified host proteins and lipids, mice defective in expression of either MARCO or SRA are immunocompromised in multiple models of infection and in vitro assays, the scavenger receptors have been demonstrated to bind bacteria and to enhance pro-inflammatory signalling to many bacterial lung pathogens; however their importance in Mycobacterium tuberculosis infection, is less clear.
  
  
  METHODS
  To determine whether polymorphisms in either SRA or MARCO were associated with tuberculosis, a case-control study of was performed. DNA samples from newly-detected, smear-positive, pulmonary tuberculosis cases were collected from The Gambia. Controls for this study consisted of DNA from cord bloods obtained from routine births at local Gambian health clinics. Informed written consent was obtained from patients or their parents or guardians. Ethical approval was provided by the joint The Gambian Government/MRC Joint Ethics Committee.
  
  
  RESULTS
  We studied the frequencies of 25 polymorphisms of MSR1 (SRA) and 22 in MARCO in individuals with tuberculosis (n=1284) and matched controls (n=1349). No SNPs within the gene encoding or within 1 kb of the promoter sequence of MSR1 were associated with either susceptibility or resistance to tuberculosis. Three SNPs in MARCO (rs4491733, Mantel-Haenszel 2x2 χ2 = 6.5, p = 0.001, rs12998782, Mantel-Haenszel 2x2 χ2 = 6.59, p = 0.001, rs13389814 Mantel-Haenszel 2x2 χ2 = 6.9, p = 0.0009) were associated with susceptibility to tuberculosis and one (rs7559955, Mantel-Haenszel 2x2 χ2 = 6.9, p = 0.0009) was associated with resistance to tuberculosis.
  
  
  CONCLUSIONS
  These findings identify MARCO as a potentially important receptor in the host response to tuberculosis.
authors.affiliation: McMaster Immunology Research Centre, McMaster University, Hamilton, ON, L8S 4K1, Canada. bowdish@mcmaster.ca
authors.forename: Dawn Me
authors.initials: DM
authors.lastname: Bowdish
authors.forename: Kaori
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Lack
authors.forename: Philip C
authors.initials: PC
authors.lastname: Hill
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sirugo
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Newport
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
authors.forename: Adrian Vs
authors.initials: AV
authors.lastname: Hill
authors.forename: Fredrick O
authors.initials: FO
authors.lastname: Vannberg
mesh_terms: D016022:Case-Control Studies; D019295:Computational Biology; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005714:Gambia / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007438:Introns; D016015:Logistic Models; D008264:Macrophages / Q000378:metabolism; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011971:Receptors, Immunologic / Q000235:genetics*; D051117:Scavenger Receptors, Class A / Q000235:genetics; D017422:Sequence Analysis, DNA; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology* / Q000235:genetics*
chemical_list: C490460:MARCO protein, human; C495139:MSR1 protein, human; D011971:Receptors, Immunologic; D051117:Scavenger Receptors, Class A; D004247:DNA