title: Genetic variation in the scavenger receptor MARCO and its association with chronic obstructive pulmonary disease and lung infection in 10,604 individuals.
abstract: BACKGROUND
  MARCO (macrophage receptor with collagenous structure) is a dominant receptor for unopsonized particles and bacteria in the lungs. Reduced function of this receptor due to genetic variation may be associated with susceptibility to chronic obstructive pulmonary disease (COPD) and lung infection.
  
  
  OBJECTIVE
  To identify novel genetic variants in MARCO that are associated with reduced lung function, or increased risk of COPD or lung infection.
  
  
  METHODS
  We first screened 760 individuals with extreme lung phenotypes in a large general population study to identify novel variants in the MARCO gene. We next genotyped the entire cohort consisting of 10,604 individuals to assess the clinical relevance of these variants.
  
  
  RESULTS
  We identified 4 novel (R124H, K201N, P303L and G340W) and 5 previously described (H101Q, F282S, G319V, K387Q and E511D) non-synonymous variants. When screening the entire cohort for these variants, we found low minor allele frequencies ranging from 0.005 to 5%. None of the individual MARCO genotypes were associated with reduced lung function, or risk of COPD or lung infection. H101Q heterozygotes had an increased odds ratio for sepsis of 2.2 (95% CI: 1.1-4.4) compared to non-carriers, but none of the other MARCO genotypes were associated with the risk of sepsis.
  
  
  CONCLUSIONS
  We identified 9 non-synonymous variants in the MARCO gene and showed that these variants are not major risk factors for COPD or lung infection in the Danish population. H101Q heterozygotes had increased sepsis risk, but further research is required to confirm this finding. This study is the first to examine genetic variants in MARCO and the risk of COPD and infections in humans.
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Copenhagen, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Thomsen
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.forename: Lester
authors.initials: L
authors.lastname: Kobzik
authors.forename: Morten
authors.initials: M
authors.lastname: Dahl
mesh_terms: D001991:Bronchitis / Q000235:genetics*; D003718:Denmark; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D016015:Logistic Models; D011014:Pneumonia / Q000235:genetics*; D016133:Polymerase Chain Reaction; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics*; D018805:Sepsis / Q000235:genetics*
chemical_list: C490460:MARCO protein, human; D011971:Receptors, Immunologic