Elizabeth T Jensen1, Jonathan T Kuhl2, Lisa J Martin3, Carl D Langefeld4, Evan S Dellon5, Marc E Rothenberg6. 1. Department of Epidemiology and Prevention, Wake Forest University Public Health Sciences, Winston-Salem, NC; Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC. Electronic address: ejensen@wakehealth.edu. 2. Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 3. Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 4. Department of Biostatistical Sciences, Wake Forest University Public Health Sciences, Winston-Salem, NC. 5. Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC; Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC. 6. Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio. Electronic address: Rothenberg@cchmc.org.
Abstract
BACKGROUND: Although eosinophilic esophagitis (EoE) is associated with certain gene variants, the rapidly increasing incidence of EoE suggests that environmental factors contribute to disease development. OBJECTIVE: We tested for gene-environment interaction between EoE-predisposing polymorphisms (within TSLP, LOC283710/KLF13, CAPN14, CCL26, and TGFB) and implicated early-life factors (antibiotic use in infancy, cesarean delivery, breast-feeding, neonatal intensive care unit [NICU] admission, and absence of pets in the home). METHODS: We conducted a case-control study using hospital-based cases (n = 127) and control subjects representative of the hospital catchment area (n = 121). We computed case-only interaction tests and in secondary analyses evaluated the combined and independent effects of genotype and environmental factors on the risk of EoE. RESULTS: Case-only analyses identified interactions between rs6736278 (CAPN14) and breast-feeding (P = .02) and rs17815905 (LOC283710/KLF13) and NICU admission (P = .02) but not with any of the factors examined. Case-control analyses suggested that disease risk might be modifiable in subjects with certain gene variants. In particular, breast-feeding in those with the susceptibility gene variant at rs6736278 (CAPN14) reduced the risk of EoE (adjusted odds ratio, 0.08; 95% CI, 0.01-0.59). Admission to the NICU in those without the susceptibility gene variant at rs17815905 (LOC283710/KLF13) significantly increased the risk of having disease (adjusted odds ratio, 4.83; 95% CI, 1.49-15.66). CONCLUSIONS: The interplay of gene (CAPN14 and LOC283710/KLF13) and early-life environment factors (breast-feeding and NICU admission) might contribute to EoE susceptibility.
BACKGROUND: Although eosinophilic esophagitis (EoE) is associated with certain gene variants, the rapidly increasing incidence of EoE suggests that environmental factors contribute to disease development. OBJECTIVE: We tested for gene-environment interaction between EoE-predisposing polymorphisms (within TSLP, LOC283710/KLF13, CAPN14, CCL26, and TGFB) and implicated early-life factors (antibiotic use in infancy, cesarean delivery, breast-feeding, neonatal intensive care unit [NICU] admission, and absence of pets in the home). METHODS: We conducted a case-control study using hospital-based cases (n = 127) and control subjects representative of the hospital catchment area (n = 121). We computed case-only interaction tests and in secondary analyses evaluated the combined and independent effects of genotype and environmental factors on the risk of EoE. RESULTS: Case-only analyses identified interactions between rs6736278 (CAPN14) and breast-feeding (P = .02) and rs17815905 (LOC283710/KLF13) and NICU admission (P = .02) but not with any of the factors examined. Case-control analyses suggested that disease risk might be modifiable in subjects with certain gene variants. In particular, breast-feeding in those with the susceptibility gene variant at rs6736278 (CAPN14) reduced the risk of EoE (adjusted odds ratio, 0.08; 95% CI, 0.01-0.59). Admission to the NICU in those without the susceptibility gene variant at rs17815905 (LOC283710/KLF13) significantly increased the risk of having disease (adjusted odds ratio, 4.83; 95% CI, 1.49-15.66). CONCLUSIONS: The interplay of gene (CAPN14 and LOC283710/KLF13) and early-life environment factors (breast-feeding and NICU admission) might contribute to EoE susceptibility.
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