Circulating microRNAs and hepcidin as predictors of iron homeostasis and anemia among school children: a biochemical and cross-sectional survey analysis

Abstract

Background: MicroRNAs (miRNAs) can control several biological processes. Thus, the existence of these molecules plays a significant role in regulating human iron metabolism or homeostasis.

Purpose: The study aimed to determine the role of circulating microRNAs and hepcidin in controlling iron homeostasis and evaluating possible anemia among school children.

Methods: The study was based on a biochemical and cross-sectional survey study that included three hundred fifty school children aged 12-18 years old. RT-PCR and immunoassay analysis were accomplished to estimate iron concentration, Hgb, serum ferritin (SF), soluble transferrin receptor (sTfR), total body iron stores (TIBs), total oxidative stress (TOS), total antioxidant capacity (TAC), α-1-acid glycoprotein (AGP), high sensitive C-reactive protein (hs-CRP), and miRNAs; miR-146a, miR-129b, and miR-122 in 350 school adolescents.

Results: Iron disorders were cross-sectionally predicted in 28.54% of the study population; they were classified into 14.26% with ID, 5.7% with IDA, and 8.6% with iron overload. The overall proportion of iron depletion was significantly higher in girls (20.0%) than in boys (8.6%). MicroRNAs; miR-146a, miR-125b, and miR-122 were significantly upregulated with lower hepcidin expression in adolescence with ID and IDA compared to iron-overloaded subjects, whereas downregulation of these miRNAs was linked with higher hepcidin. Also, a significant correlation was recorded between miRNAs, hepcidin levels, AGP, hs-CRP, TAC, and other iron-related indicators.

Conclusion: Molecular microRNAs such as miR-146a, miR-125b, and miR-122 were shown to provide an additional means of controlling or regulating cellular iron uptake or metabolism either via the oxidative stress pathway or regulation of hepcidin expression via activating genes encoding Hfe and Hjv activators, which promote iron regulation. Thus, circulating miRNAs as molecular markers and serum hepcidin could provide an additional means of controlling or regulating cellular iron and be associated as valuable markers in diagnosing and treating cases with different iron deficiencies.

Keywords: Acute phase reaction; Adolescence; Iron status; Micro-RNAs; School children; Subclinical inflammation.

Fig. 1

Molecular changes in oxidative stress TOS and TAC (A), inflammatory markers; AGP and hs-CRP (B), and miRNAs expression; miR-146 a, miR-125 b, miR-122 (C) in iron deficiency and control school children aged 12–18 years. Iron deficiency was reported according to gender (D). There were significant increase and decrease in the expression levels of TOS and TAC in students with ID, IDA, and iron overload status (**P = 0.01; ***P = 0.001) [A]. Also, AGP and hs-CRP as markers of inflammation were significantly increased in subjects with iron overload compared to those of iron disorders; ID, IDA, and controls, respectively (**P = 0.01, ***P = 0.001) (B). Expression of miRNAs; miR-146a and miR-125b, and miR-122 were significantly upregulated in subjects with ID, IDA, and downregulated in iron overloaded subjects compared to expression levels obtained in control subjects respectively (**P = 0.01, ***P = 0.001) (C). Iron deficiency was significantly higher in girls (20%; P = 0.01) than in boys (8.6%; P = 0.01) as compared to normal controls (D). Abbreviation: BMI: body mass index; sTfR, soluble transferrin receptor; TBIS, total boy iron store; TOS, total oxidative stress; TAC, total antioxidant capacity; hs-CRP, high sensitivity C-reactive protein; AGP, α-1-acid glycoprotein; NI: normal iron (iron conc.;75–175 μg/dl); ID: iron deficiency (iron conc.; < 75 μg/dl l); IDA: iron deficiency anemia (iron conc.; < 75 μg/dl l; hemoglobin < 120 g/L, and ferritin < 15 μg/L); IO: iron overload (iron conc.; ˃175 μg/dl). Variables were considered significantly different at P < 0.05