title: The TGFβ1 Promoter SNP C-509T and Food Sensitization Promote Esophageal Remodeling in Pediatric Eosinophilic Esophagitis.
abstract: BACKGROUND
  Eosinophilic esophagitis (EoE) is a chronic antigen mediated disease associated with substantial esophageal remodeling and fibrosis. The functional TGFβ1 promoter SNP C-509 associates with renal fibrosis and asthma. The effect of TGFβ1 genotype and EoE severity or potential gene-environment interactions have not been previously reported in EoE.
  
  
  METHODS
  Genotype at TGFβ1 C-509T and remodeling was analyzed in 144 subjects with EoE. The severity of remodeling and inflammation was analyzed in the context of IgE sensitization to food antigens and C-509T genotype.
  
  
  RESULTS
  The TGFβ1 promoter C-509 genotypes CC, CT, and TT were 35%, 52%, and 13%, respectively. Sixty-six percent of subjects were sensitized to foods by positive skin prick test (SPT) or serum specific IgE. TT genotype subjects had significantly more TGFβ1 (CC subjects = 1300 per mm2; TT = 2250 per mm2) (p<0.05) and tryptase (CC subjects = 145 per mm2: TT = 307 per mm2) (p<0.05) positive cells and higher epithelial remodeling scores (2.4 vs 3.7, p<0.001) than CC subjects. The differences in TGFβ1 and tryptase positive cells as well as fibrosis were significantly increased when there was concurrent food sensitization. Food sensitization alone did not associate with any parameters of inflammation or remodeling.
  
  
  CONCLUSIONS
  Our data support a gene-environment interaction between food and genotype at C-509 that modulates disease severity in EoE. Since EoE subjects often continue to consume foods to which they are sensitized, these findings may have clinical relevance for disease management.
authors.affiliation: Division of Allergy, Immunology, University of California San Diego, La Jolla, California, United States of America.|Center for Infection, Immunity, and Inflammation, University of California San Diego, La Jolla, California, United States of America.|Department of Pediatrics, University of California San Diego, La Jolla, California, Rady Children's Hospital, San Diego, California, United States of America.
authors.forename: Renee
authors.initials: R
authors.lastname: Rawson
authors.affiliation: Division of Allergy, Immunology, University of California San Diego, La Jolla, California, United States of America.|Center for Infection, Immunity, and Inflammation, University of California San Diego, La Jolla, California, United States of America.|Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Arjun
authors.initials: A
authors.lastname: Anilkumar
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, California, Rady Children's Hospital, San Diego, California, United States of America.|Department of Pathology, University of California San Diego, La Jolla, California, Rady Children's Hospital, San Diego, California, United States of America.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Newbury
authors.affiliation: Department of Computer Science and Engineering, University of California, San Diego, La Jolla, California.
authors.forename: Vineet
authors.initials: V
authors.lastname: Bafna
authors.affiliation: Division of Allergy, Immunology, University of California San Diego, La Jolla, California, United States of America.|Department of Pediatrics, University of California San Diego, La Jolla, California, Rady Children's Hospital, San Diego, California, United States of America.
authors.forename: Melissa
authors.initials: M
authors.lastname: Aquino
authors.affiliation: Division of Allergy, Immunology, University of California San Diego, La Jolla, California, United States of America.|Department of Pediatrics, University of California San Diego, La Jolla, California, Rady Children's Hospital, San Diego, California, United States of America.
authors.forename: Jacob
authors.initials: J
authors.lastname: Palmquist
authors.affiliation: Division of Allergy, Immunology, University of California San Diego, La Jolla, California, United States of America.|Center for Infection, Immunity, and Inflammation, University of California San Diego, La Jolla, California, United States of America.|Department of Pediatrics, University of California San Diego, La Jolla, California, Rady Children's Hospital, San Diego, California, United States of America.|Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Hal M
authors.initials: HM
authors.lastname: Hoffman
authors.affiliation: Division of Allergy, Immunology, University of California San Diego, La Jolla, California, United States of America.|Center for Infection, Immunity, and Inflammation, University of California San Diego, La Jolla, California, United States of America.|Department of Pediatrics, University of California San Diego, La Jolla, California, Rady Children's Hospital, San Diego, California, United States of America.
authors.forename: James L
authors.initials: JL
authors.lastname: Mueller
authors.affiliation: Division of Pediatric Gastroenterology and Nutrition, University of California San Diego, La Jolla, California, Rady Children's Hospital, San Diego, California, United States of America.|Department of Pediatrics, University of California San Diego, La Jolla, California, Rady Children's Hospital, San Diego, California, United States of America.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Dohil
authors.affiliation: Division of Allergy, Immunology, University of California San Diego, La Jolla, California, United States of America.|Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: David H
authors.initials: DH
authors.lastname: Broide
authors.affiliation: Division of Allergy, Immunology, University of California San Diego, La Jolla, California, United States of America.|Center for Infection, Immunity, and Inflammation, University of California San Diego, La Jolla, California, United States of America.|Department of Pediatrics, University of California San Diego, La Jolla, California, Rady Children's Hospital, San Diego, California, United States of America.|Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Seema S
authors.initials: SS
authors.lastname: Aceves
mesh_terms: D002648:Child; D002675:Child, Preschool; D057765:Eosinophilic Esophagitis / Q000235:genetics* / Q000473:pathology; D004947:Esophagus / Q000473:pathology*; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012720:Severity of Illness Index; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D053773:Transforming Growth Factor beta1; D007073:Immunoglobulin E