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). CONCLUSION: 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.
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). CONCLUSION: 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: Dan Nicolae; Nancy J Cox; Lucille A Lester; Daniel Schneider; Zheng Tan; Christine Billstrand; Susan Kuldanek; Joseph Donfack; Paul Kogut; Nina M Patel; Jeffrey Goodenbour; Timothy Howard; Raoul Wolf; Gerard H Koppelman; Steven R White; Rodney Parry; Dirkje S Postma; Deborah Meyers; Eugene R Bleecker; Joan S Hunt; Julian Solway; Carole Ober Journal: Am J Hum Genet Date: 2004-12-20 Impact factor: 11.025
Authors: Steven R White; Jessie Nicodemus-Johnson; Bharathi Laxman; Darcy R Denner; Edward T Naureckas; D Kyle Hogarth; Randi Stern; Alexa Minc; Julian Solway; Anne Sperling; Carole Ober Journal: J Allergy Clin Immunol Date: 2017-03-28 Impact factor: 10.793
Authors: Darcy R Denner; Naseer Sangwan; Julia B Becker; D Kyle Hogarth; Justin Oldham; Jamee Castillo; Anne I Sperling; Julian Solway; Edward T Naureckas; Jack A Gilbert; Steven R White Journal: J Allergy Clin Immunol Date: 2015-11-25 Impact factor: 10.793
Authors: Jessie Nicodemus-Johnson; Rachel A Myers; Noburu J Sakabe; Debora R Sobreira; Douglas K Hogarth; Edward T Naureckas; Anne I Sperling; Julian Solway; Steven R White; Marcelo A Nobrega; Dan L Nicolae; Yoav Gilad; Carole Ober Journal: JCI Insight Date: 2016-12-08
Authors: Holly Rutledge; Jeanette Baran-Gale; Fernando Pardo-Manuel de Villena; Elissa J Chesler; Gary A Churchill; Praveen Sethupathy; Samir N P Kelada Journal: BMC Genomics Date: 2015-08-25 Impact factor: 3.969