title: A polymorphism in HLA-G modifies statin benefit in asthma.
abstract: Several reports have shown that statin treatment benefits patients with asthma; however, inconsistent effects have been observed. The mir-152 family (148a, 148b and 152) has been implicated in asthma. These microRNAs suppress HLA-G expression, and rs1063320, a common SNP in the HLA-G 3'UTR that is associated with asthma risk, modulates miRNA binding. We report that statins upregulate mir-148b and 152, and affect HLA-G expression in an rs1063320-dependent fashion. In addition, we found that individuals who carried the G minor allele of rs1063320 had reduced asthma-related exacerbations (emergency department visits, hospitalizations or oral steroid use) compared with non-carriers (P=0.03) in statin users ascertained in the Personalized Medicine Research Project at the Marshfield Clinic (n=421). These findings support the hypothesis that rs1063320 modifies the effect of statin benefit in asthma, and thus may contribute to variation in statin efficacy for the management of this disease.
authors.affiliation: Atherosclerosis Research, Children's Hospital Oakland Research Institute, Oakland, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Naidoo
authors.affiliation: Department of Population Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Wu
authors.affiliation: Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Brilliant
authors.affiliation: 1] Department of Medical Bioinformatics, Vanderbilt University School of Medicine, Nashville, TN, USA [2] Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: J
authors.initials: J
authors.lastname: Denny
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: C
authors.initials: C
authors.lastname: Ingram
authors.affiliation: Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA.
authors.forename: T E
authors.initials: TE
authors.lastname: Kitchner
authors.affiliation: Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Linneman
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: McGeachie
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Roden
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Shaffer
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Shah
authors.affiliation: 1] Department of Medicine, Vanderbilt University, Nashville, TN, USA [2] Department of Cardiology, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Weeke
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Weiss
authors.affiliation: School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.affiliation: Atherosclerosis Research, Children's Hospital Oakland Research Institute, Oakland, CA, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Medina
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000483:Alleles; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D059951:HLA-G Antigens / Q000235:genetics*; D056945:Hep G2 Cells; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk
chemical_list: D020413:3' Untranslated Regions; D059951:HLA-G Antigens; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D035683:MicroRNAs