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Genetic analyses of chr11p15.5 region identify MUC5AC-MUC5B associated with asthma-related phenotypes.
Li, Xingnan; Li, Huashi; Christenson, Stephanie A; Castro, Mario; Denlinger, Loren C; Erzurum, Serpil C; Fahy, John V; Gaston, Benjamin M; Israel, Elliot; Jarjour, Nizar N; Levy, Bruce D; Mauger, David T; Moore, Wendy C; Zein, Joe; Kaminski, Naftali; Wenzel, Sally E; Woodruff, Prescott G; Bleecker, Eugene R; Meyers, Deborah A.
Afiliação
  • Li X; Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, Tucson, AZ, USA.
  • Li H; Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, Tucson, AZ, USA.
  • Christenson SA; Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of California at San Francisco, San Francisco, CA, USA.
  • Castro M; Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, KS, USA.
  • Denlinger LC; Department of Medicine, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA.
  • Erzurum SC; Lerner Research Institute and the Respiratory Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Fahy JV; Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of California at San Francisco, San Francisco, CA, USA.
  • Gaston BM; Wells Center for Pediatric Research and Riley Hospital for Children, Indiana University, Indianapolis, IN, USA.
  • Israel E; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Jarjour NN; Department of Medicine, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA.
  • Levy BD; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Mauger DT; Department of Public Health Sciences, College of Medicine, Penn State University, Hershey, PA, USA.
  • Moore WC; Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Zein J; Lerner Research Institute and the Respiratory Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Kaminski N; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
  • Wenzel SE; Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA.
  • Woodruff PG; Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of California at San Francisco, San Francisco, CA, USA.
  • Bleecker ER; Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, Tucson, AZ, USA.
  • Meyers DA; Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, Tucson, AZ, USA.
J Asthma ; 60(10): 1824-1835, 2023 10.
Article em En | MEDLINE | ID: mdl-36946148
OBJECTIVE: Genome-wide association studies (GWASs) have identified single nucleotide polymorphisms (SNPs) in chr11p15.5 region associated with asthma and idiopathic interstitial pneumonias (IIPs). We sought to identify functional genes for asthma by combining SNPs and mRNA expression in bronchial epithelial cells (BEC) in the Severe Asthma Research Program (SARP). METHODS: Correlation analyses of mRNA expression of six candidate genes (AP2A2, MUC6, MUC2, MUC5AC, MUC5B, and TOLLIP) and asthma phenotypes were performed in the longitudinal cohort (n = 156) with RNAseq in BEC, and replicated in the cross-sectional cohort (n = 155). eQTL (n = 114) and genetic association analysis of asthma severity (426 severe vs. 531 non-severe asthma) were performed, and compared with previously published GWASs of IIPs and asthma. RESULTS: Higher expression of AP2A2 and MUC5AC and lower expression of MUC5B in BEC were correlated with asthma, asthma exacerbations, and T2 biomarkers (P < 0.01). SNPs associated with asthma and IIPs in previous GWASs were eQTL SNPs for MUC5AC, MUC5B, or TOLLIP, however, they were not in strong linkage disequilibrium. The risk alleles for asthma or protective alleles for IIPs were associated with higher expression of MUC5AC and lower expression of MUC5B. rs11603634, rs12788104, and rs28415845 associated with moderate-to-severe asthma or adult onset asthma in previous GWASs were not associated with asthma severity (P > 0.8). CONCLUSIONS: SNPs associated with asthma in chr11p15.5 region are not associated with asthma severity neither with IIPs. Higher expression of MUC5AC and lower expression of MUC5B are risk for asthma but protective for IIPs.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Asma Tipo de estudo: Observational_studies / Prevalence_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Asthma Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Asma Tipo de estudo: Observational_studies / Prevalence_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Asthma Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos