title: Maternal asthma and microRNA regulation of soluble HLA-G in the airway.
abstract: BACKGROUND
  We previously reported an interaction between maternal asthma and the child's HLA-G genotype on the child's subsequent risk for asthma. The implicated single nucleotide polymorphism at +3142 disrupted a target site for the microRNA (miR)-152 family. We hypothesized that the interaction effect might be mediated by these miRs.
  
  
  OBJECTIVE
  The objective of this study was to test this hypothesis in adults with asthma who are a subset of the same subjects who participated in our earlier family-based studies.
  
  
  METHODS
  We measured soluble HLA-G (sHLA-G) concentrations in bronchoalveolar lavage fluid (n = 36) and plasma (n = 57) from adult asthmatic subjects with and without a mother with asthma, and HLA-G and miR-152 family (miR-148a, miR-148b, and miR-152) transcript levels in airway epithelial cells from the same subjects.
  
  
  RESULTS
  miR-148b levels were significantly increased in airway epithelial cells from asthmatic subjects with an asthmatic mother compared with those seen in asthmatic subjects without an asthmatic mother, and +3142 genotypes were associated with sHLA-G concentrations in bronchoalveolar lavage fluid among asthmatic subjects with an asthmatic mother but not among those with a nonasthmatic mother. Neither effect was observed in the plasma (sHLA-G) or white blood cells (miRNA).
  
  
  CONCLUSIONS
  These combined results are consistent with +3142 allele-specific targeting of HLA-G by the miR-152 family and support our hypothesis that miRNA regulation of sHLA-G in the airway is influenced by both the asthma status of the subject's mother and the subject's genotype. Moreover, we demonstrate that the effects of maternal asthma on the gene regulatory landscape in the airways of the mother's children persist into adulthood.
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. jnicodem@bsd.uchicago.edu
authors.forename: Jessie
authors.initials: J
authors.lastname: Nicodemus-Johnson
authors.forename: Bharathi
authors.initials: B
authors.lastname: Laxman
authors.forename: Randi K
authors.initials: RK
authors.lastname: Stern
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Sudi
authors.forename: Courtney N
authors.initials: CN
authors.lastname: Tierney
authors.forename: Lourdes
authors.initials: L
authors.lastname: Norwick
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Hogarth
authors.forename: John F
authors.initials: JF
authors.lastname: McConville
authors.forename: Edward T
authors.initials: ET
authors.lastname: Naureckas
authors.forename: Anne I
authors.initials: AI
authors.lastname: Sperling
authors.forename: Julian
authors.initials: J
authors.lastname: Solway
authors.forename: Jerry A
authors.initials: JA
authors.lastname: Krishnan
authors.forename: Dan L
authors.initials: DL
authors.lastname: Nicolae
authors.forename: Steven R
authors.initials: SR
authors.lastname: White
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
mesh_terms: D000328:Adult; D001741:Black or African American; D001249:Asthma / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005838:Genotype; D059951:HLA-G Antigens / Q000097:blood / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism; D044465:White People; D055815:Young Adult
chemical_list: D059951:HLA-G Antigens; C550856:MIRN152 microRNA, human; D035683:MicroRNAs
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