Dataset Information

Biological marks of early-life socioeconomic experience is detected in the adult inflammatory transcriptome.

ABSTRACT: Consistent evidence is accumulating to link lower socioeconomic position (SEP) and poorer health, and the inflammatory system stands out as a potential pathway through which socioeconomic environment is biologically embedded. Using bloodderived genome-wide transcriptional profiles from 268 Italian participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we evaluated the association between early life, young and later adulthood SEP and the expression of 845 genes involved in human inflammatory responses. These were examined individually and jointly using several inflammatory scores. Our results consistently show that participants whose father had a manual (as compared to nonmanual) occupation exhibit, later in life, a higher inflammatory score, hence indicating an overall increased level of expression for the selected inflammatory-related genes. Adopting a life course approach, these associations remained statistically significant upon adjustment for later-in-life socioeconomic experiences. Sensitivity analyses indicated that our findings were not affected by the way the inflammatory score was calculated, and were replicated in an independent study. Our study provides additional evidence that childhood SEP is associated with a sustainable upregulation of the inflammatory transcriptome, independently of subsequent socioeconomic experiences. Our results support the hypothesis that early social inequalities impacts adult physiology.

SUBMITTER: Castagne R

PROVIDER: S-EPMC5146729 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Biological marks of early-life socioeconomic experience is detected in the adult inflammatory transcriptome.

Castagné Raphaële R Kelly-Irving Michelle M Campanella Gianluca G Guida Florence F Krogh Vittorio V Palli Domenico D Panico Salvatore S Sacerdote Carlotta C Tumino Rosario R Kleinjans Jos J de Kok Theo T Kyrtopoulos Soterios A SA Lang Thierry T Stringhini Silvia S Vermeulen Roel R Vineis Paolo P Delpierre Cyrille C Chadeau-Hyam Marc M

Scientific reports 20161209

Consistent evidence is accumulating to link lower socioeconomic position (SEP) and poorer health, and the inflammatory system stands out as a potential pathway through which socioeconomic environment is biologically embedded. Using bloodderived genome-wide transcriptional profiles from 268 Italian participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we evaluated the association between early life, young and later adulthood SEP and the expression of 845 ...[more]

PMID: 27934951

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Project description:BackgroundIron deficiency (ID) compromises the developing nervous system, including the hippocampus, resulting in later-life deficits despite iron repletion. The iron-dependent molecular changes driving these lasting deficits, and the effect of early iron repletion, are incompletely understood. Previous studies have utilized dietary models of maternal-fetal ID anemia (IDA) to address these questions; however, concurrent anemia prevents delineation of the specific role of iron.ObjectiveThe aim of the study was to isolate the effects of developmental ID on adult hippocampal gene expression and to determine if iron repletion reverses these effects in a mouse model of nonanemic hippocampal neuronal ID.MethodsNonanemic, hippocampus-specific neuronal ID was generated by using a Tet-OFF dominant negative transferrin receptor (DN-TFR1) mouse model that impairs cellular iron uptake. Hippocampal ID was reversed with doxycycline at postnatal day 21 (P21) in a subset of mice to create 2 experimental groups, chronically iron-deficient and formerly iron-deficient mice, which were compared with their respective doxycycline-treated and untreated iron-sufficient controls. RNA from adult male hippocampi was sequenced. Paired-end reads were analyzed for differential expression. Differentially expressed genes were analyzed in Ingenuity Pathway Analysis.ResultsA total of 346 genes were differentially expressed in adult, chronically iron-deficient hippocampi compared with controls. ID dysregulated genes in critical neurodevelopmental pathways, including axonal guidance, CDK5, Ephrin receptor, Rac, and Neurotrophin/Trk signaling. Iron repletion at P21 normalized adult hippocampal expression of 198 genes; however, genes involved in cAMP response element-binding protein (CREB) signaling, neurocognition, and neurologic disease remained dysregulated in adulthood.ConclusionsChronic ID during development, independent of anemia, alters the adult mouse hippocampal transcriptome. Restoring iron status during a known critical period of hippocampal neurodevelopment incompletely normalized these changes, suggesting a need for additional studies to identify the most effective timeline for iron therapy, and adjunctive treatments that can fully restore ID-induced molecular changes, particularly in human populations in whom chronic ID is endemic.

Project description:ObjectiveThis study aimed to determine the association between adolescent socioeconomic status (father's education and adolescent subjective socioeconomic status) and adult quality of life and the mediation roles of adult socioeconomic status, social capital and lifestyle (physical activity and exposure to smoke) among the "Tehran University of Medical Sciences Employees Cohort (TEC) Study" participants.MethodData of 4455 participants were derived from the Tehran University of Medical Sciences Employees Cohort (TEC) Study. In this study, the World Health Organization quality of life-BREF, the World Bank's Integrated and the International Physical Activity Questionnaire were used. Data were analyzed with structural equation modeling using SPSS Amos 24.0 program.ResultsThe mean age of the participants was 42.31 years (SD: 8.37) and most of the subjects were female (60.7%). Correlation analysis results revealed that, quality of life had a significant and positive association with adolescent subjective socioeconomic status (r = 0.169, p < 0.01) and father's education (r = 0.091, p < 0.01). A mediation model testing the direct relationship between adolescent socioeconomic status and adult socioeconomic status and quality of life, showed a positive relationship between adolescent subjective socioeconomic status (β = 0.229, p < 0.001) and father's education (β = 0.443, p < 0.001) with adult socioeconomic status. Adult socioeconomic status was positively related to quality of life (β = 0.205, p < 0.001). Adult socioeconomic status mediated the relationship between adolescent subjective socioeconomic status (β = 0.047, p < 0.01) and father's education (β = 0.091, p < 0.01) with quality of life. While adult socioeconomic status fully mediated the relationship between the father's education and quality of life, it partially mediated the adolescent subjective socioeconomic status-quality of life association. Other variables such as social capital and lifestyle did not have mediator role in a mediation model.ConclusionThis study provides the evidence for the role of adult socioeconomic status as a partial mediator between adolescent subjective socioeconomic status and quality of life. Therefore, there are several unknown mediators other than adult socioeconomic status that need to be explored in future studies.

Dataset Information

Biological marks of early-life socioeconomic experience is detected in the adult inflammatory transcriptome.

Publications

Biological marks of early-life socioeconomic experience is detected in the adult inflammatory transcriptome.

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