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Early-life environmental exposures interact with genetic susceptibility variants in pediatric patients with eosinophilic esophagitis.

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.

SUBMITTER: Jensen ET

PROVIDER: S-EPMC5803324 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Early-life environmental exposures interact with genetic susceptibility variants in pediatric patients with eosinophilic esophagitis.

Jensen Elizabeth T ET Kuhl Jonathan T JT Martin Lisa J LJ Langefeld Carl D CD Dellon Evan S ES Rothenberg Marc E ME

The Journal of allergy and clinical immunology 20171010 2

<h4>Background</h4>Although eosinophilic esophagitis (EoE) is associated with certain gene variants, the rapidly increasing incidence of EoE suggests that environmental factors contribute to disease development.<h4>Objective</h4>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] ...[more]

PMID: 29029802

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Project description:IntroductionEmerging evidence suggests a high burden of psychosocial comorbidities in patients with eosinophilic esophagitis (EoE), although factors associated with this burden have not been explored. We aimed to increase understanding of the psychosocial burden of EoE and assess factors that are associated with disease burden.MethodsWe conducted a cross-sectional study of patients with EoE (n = 87) recruited from a single-center, multidisciplinary pediatric eosinophilic gastrointestinal disorders clinic (2019-2021). Participants (aged 8-18 years) completed validated assessments during routine clinic visit to assess EoE symptoms (Pediatric Eosinophilic Esophagitis Symptom Score version 2.0), quality of life (Pediatric Quality of LIfe- Eosinophilic Esophagitis), anxiety state and trait (State-Trait Anxiety Score for Children), somatization (Child Somatic Symptoms Inventory 24), sleep disordered breathing (Pediatric Sleep Questionnaire) and, in a subset (n = 35), resilience (Connor Davidson Resilience Scale). Clinical and demographic data were collected.ResultsParticipants were at a mean (SD) age of 12.8 (3.1) years, and 26% (n = 23) were female. Shorter disease duration (6-12 months) was associated with higher symptom burden ( P = 0.03), somatization ( P < 0.01), and anxiety (State-Trait Anxiety Score for Children Trait P < 0.01) scores. Participants with neurodevelopmental comorbidities had higher anxiety trait, somatization, sleep disordered breathing, and lower quality of life ( P < 0.01 for all). Symptom burden was significantly associated with increased somatic symptoms (adjusted β [aβ] = 0.34; 95% confidence interval 0.23-0.45) and decreased quality of life (aβ = -0.42; 95% confidence interval -0.59 to -0.25) but not state anxiety, trait anxiety, or disordered sleep breathing.DiscussionPediatric patients with a recent diagnosis of EoE can experience higher EoE symptoms, somatization, and anxiety when compared with those with a longer-standing diagnosis. Patients earlier in their diagnosis and with neurodevelopmental disorders may experience increased somatization and anxiety that may warrant additional support services.

Project description:BackgroundGrowing evidence exists about the fetal and environmental origins of hypertension, but mainly limited to single-exposure studies. The exposome has been proposed as a more holistic approach by studying many exposures simultaneously.ObjectivesThis study aims to evaluate the association between a wide range of prenatal and postnatal exposures and blood pressure (BP) in children.MethodsSystolic and diastolic BP were measured among 1,277 children from the European HELIX (Human Early-Life Exposome) cohort aged 6 to 11 years. Prenatal (n = 89) and postnatal (n = 128) exposures include air pollution, built environment, meteorology, natural spaces, traffic, noise, chemicals, and lifestyles. Two methods adjusted for confounders were applied: an exposome-wide association study considering the exposures independently, and the deletion-substitution-addition algorithm considering all the exposures simultaneously.ResultsDecreases in systolic BP were observed with facility density (β change for an interquartile-range increase in exposure: -1.7 mm Hg [95% confidence interval (CI): -2.5 to -0.8 mm Hg]), maternal concentrations of polychlorinated biphenyl 118 (-1.4 mm Hg [95% CI: -2.6 to -0.2 mm Hg]) and child concentrations of dichlorodiphenyldichloroethylene (DDE: -1.6 mm Hg [95% CI: -2.4 to -0.7 mm Hg]), hexachlorobenzene (-1.5 mm Hg [95% CI: -2.4 to -0.6 mm Hg]), and mono-benzyl phthalate (-0.7 mm Hg [95% CI: -1.3 to -0.1 mm Hg]), whereas increases in systolic BP were observed with outdoor temperature during pregnancy (1.6 mm Hg [95% CI: 0.2 to 2.9 mm Hg]), high fish intake during pregnancy (2.0 mm Hg [95% CI: 0.4 to 3.5 mm Hg]), maternal cotinine concentrations (1.2 mm Hg [95% CI: -0.3 to 2.8 mm Hg]), and child perfluorooctanoate concentrations (0.9 mm Hg [95% CI: 0.1 to 1.6 mm Hg]). Decreases in diastolic BP were observed with outdoor temperature at examination (-1.4 mm Hg [95% CI: -2.3 to -0.5 mm Hg]) and child DDE concentrations (-1.1 mm Hg [95% CI: -1.9 to -0.3 mm Hg]), whereas increases in diastolic BP were observed with maternal bisphenol-A concentrations (0.7 mm Hg [95% CI: 0.1 to 1.4 mm Hg]), high fish intake during pregnancy (1.2 mm Hg [95% CI: -0.2 to 2.7 mm Hg]), and child copper concentrations (0.9 mm Hg [95% CI: 0.3 to 1.6 mm Hg]).ConclusionsThis study suggests that early-life exposure to several chemicals, as well as built environment and meteorological factors, may affect BP in children.

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Early-life environmental exposures interact with genetic susceptibility variants in pediatric patients with eosinophilic esophagitis.

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Early-life environmental exposures interact with genetic susceptibility variants in pediatric patients with eosinophilic esophagitis.

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