Association of Plasma Low-Density Lipoprotein Receptor-Related Protein-1 (LRP1) with Undernutrition: A Case-Control Study in Bangladeshi Adults

Hasan, Md. Mehedi; Fahim, Shah Mohammad; Das, Subhasish; Gazi, Md. Amran; Mahfuz, Mustafa; Ahmed, Tahmeed

doi:10.21203/rs.3.rs-56409/v1

Cited by 2 publications

(1 citation statement)

References 25 publications

(51 reference statements)

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“…S8e. Here we observed the association of downregulated H3K4me3 and H3K27ac regions with NOTCH signaling genes, a pathway crucial in development, whereas H3K4me3 regions upregulated within H3K27ac regions show association with genes involved in the acute inflammatory response as well as vitamin B12 metabolism, a component of one-carbon metabolism with a previously reported association with stunting (30).…”

Section: Resultssupporting

confidence: 81%

Histone H3 lysine 27 acetylation profile undergoes two global shifts in undernourished children and suggests one-carbon metabolite insufficiency

Kupkova

Haque

et al. 2021

Preprint

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Background: Stunting is a condition in which a child does not reach their full growth potential due to chronic undernutrition. It arises during the first two years of a child's life and is associated with developmental deficiencies and life-long health problems. Current interventions provide some benefit, but new approaches to prevention and treatment grounded in a molecular understanding of stunting are needed. Epigenetic analyses are critical as they can provide insight into how signals from a poor environment lead to changes in cell function. Results: Here we profiled histone H3 acetylation on lysine 27 (H3K27ac) in peripheral blood mononuclear cells (PBMCs) of 18-week-old and one-year-old children living in an urban slum in Dhaka, Bangladesh. We show that 18-week-old children destined to become stunted have elevated levels of H3K27ac overall, functional analysis of which indicates activation of the immune system and stress response pathways as a primary response to a poor environment with high pathogen load. Conversely, overt stunting at 1-year-of age is associated with globally reduced H3K27ac that is indicative of metabolic rewiring and downregulation of the immune system and DNA repair pathways that are likely secondary responses to chronic exposure to a poor environment with limited nutrients. The results from one-year-old children also point toward deficiency in one-carbon metabolism, which is further supported by integrative analysis with results from histone H3 trimethylation on lysine 4 (H3K4me3). Conclusions: The epigenomes of stunted children undergo two global changes in H3K27ac within their first year of life, which are associated with probable initial hyperactive immune responses followed by reduced metabolic capacity. Limitation of one-carbon metabolites may play a key role in the development of stunting.

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Section: Resultssupporting

confidence: 81%

Histone H3 lysine 27 acetylation profile undergoes two global shifts in undernourished children and suggests one-carbon metabolite insufficiency

Kupkova

Haque

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

Histone H3 lysine 27 acetylation profile undergoes two global shifts in undernourished children and suggests altered one-carbon metabolism

et al. 2021

View full text Add to dashboard Cite

Background Stunting is a condition in which a child does not reach their full growth potential due to chronic undernutrition. It arises during the first 2 years of a child’s life and is associated with developmental deficiencies and life-long health problems. Current interventions provide some benefit, but new approaches to prevention and treatment grounded in a molecular understanding of stunting are needed. Epigenetic analyses are critical as they can provide insight into how signals from a poor environment lead to changes in cell function. Results Here we profiled histone H3 acetylation on lysine 27 (H3K27ac) in peripheral blood mononuclear cells (PBMCs) of 18-week-old (n = 14) and 1-year-old children (n = 22) living in an urban slum in Dhaka, Bangladesh. We show that 18-week-old children destined to become stunted have elevated levels of H3K27ac overall, functional analysis of which indicates activation of the immune system and stress response pathways as a primary response to a poor environment with high pathogen load. Conversely, overt stunting at 1-year-of age is associated with globally reduced H3K27ac that is indicative of metabolic rewiring and downregulation of the immune system and DNA repair pathways that are likely secondary responses to chronic exposure to a poor environment with limited nutrients. Among processes altered in 1-year-old children, we identified one-carbon metabolism, the significance of which is supported by integrative analysis with results from histone H3 trimethylation on lysine 4 (H3K4me3). Together, these results suggest altered one-carbon metabolism in this population of stunted children. Conclusions The epigenomes of stunted children undergo two global changes in H3K27ac within their first year of life, which are associated with probable initial hyperactive immune responses followed by reduced metabolic capacity. Limitation of one-carbon metabolites may play a key role in the development of stunting. Trial registration ClinicalTrials.gov NCT01375647. Registered 17 June 2011, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01375647.

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Association of Plasma Low-Density Lipoprotein Receptor-Related Protein-1 (LRP1) with Undernutrition: A Case-Control Study in Bangladeshi Adults

Cited by 2 publications

References 25 publications

Histone H3 lysine 27 acetylation profile undergoes two global shifts in undernourished children and suggests one-carbon metabolite insufficiency

Histone H3 lysine 27 acetylation profile undergoes two global shifts in undernourished children and suggests one-carbon metabolite insufficiency

Histone H3 lysine 27 acetylation profile undergoes two global shifts in undernourished children and suggests altered one-carbon metabolism

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