scholarly journals Association of SNPs within TMPRSS6 and BMP2 genes with iron deficiency status in Saudi Arabia

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0257895
Author(s):  
Osama M. Al-Amer ◽  
Atif Abdulwahab A. Oyouni ◽  
Mohammed Ali Alshehri ◽  
Abdulrahman Alasmari ◽  
Othman R. Alzahrani ◽  
...  

Background Globally, iron-deficiency anemia (IDA) remains a major health obstacle. This health condition has been identified in 47% of pre-school students (aged 0 to 5 years), 42% of pregnant females, and 30% of non-pregnant females (aged 15 to 50 years) worldwide according to the WHO. Environmental and genetic factors play a crucial role in the development of IDA; genetic testing has revealed the association of a number of polymorphisms with iron status and serum ferritin. Aim The current study aims to reveal the association of TMPRSS6 rs141312 and BMP2 rs235756 with the iron status of females in Saudi Arabia. Methods A cohort of 108 female university students aged 18–25 years was randomly selected to participate: 50 healthy and 58 classified as iron deficient. A 3–5 mL sample of blood was collected from each one and analyzed based on hematological and biochemical iron status followed by genotyping by PCR. Results The genotype distribution of TMPRSS6 rs141312 was 8% (TT), 88% (TC) and 4% (CC) in the healthy group compared with 3.45% (TT), 89.66% (TC) and 6.89% (CC) in the iron-deficient group (P = 0.492), an insignificant difference in the allelic distribution. The genotype distribution of BMP2 rs235756 was 8% (TT), 90% (TC) and 2% (CC) in the healthy group compared with 3.45% (TT), 82.76% (TC) and 13.79% (CC) in iron-deficient group (P = 0.050) and was significantly associated with decreased ferritin status (P = 0.050). In addition, TMPRSS6 rs141312 is significantly (P<0.001) associated with dominant genotypes (TC+CC) and increased risk of IDA while BMP2 rs235756 is significantly (P<0.026) associated with recessive homozygote CC genotypes and increased risk of IDA. Conclusion Our finding potentially helps in the early prediction of iron deficiency in females through the genetic testing.

2011 ◽  
Vol 68 (2) ◽  
pp. 130-135 ◽  
Author(s):  
Slavica Radjen ◽  
Goran Radjen ◽  
Mirjana Zivotic-Vanovic ◽  
Sonja Radakovic ◽  
Nadja Vasiljevic ◽  
...  

Background/Aim. Iron is a vital constituent of hemoglobin, myoglobin, and some mitochondrial enzymes; therefore, body iron deficiency may result in reduced aerobic capacity. The aim of this study was to evaluate the effects of daily oral iron supplementation on body iron status, and the maximal oxygen uptake (VO2max) in female athletes with latent iron deficiency, as well as with irondeficiency anemia. Methods. A total of 37 female volleyball players were included in the study. Seventeen female athletes had latent iron deficiency, and 20 ones iron deficiency anemia. Both groups were divided into the experimental and the control group. The experimental groups received a daily oral iron supplement (200 mg ferrous sulfate), for a two-month training course. Iron status was determined by serum parameters as follows: red blood cells count, hemoglobin concentration, serum iron and ferritin levels, an unsaturated iron binding capacity, total iron binding capacity and transferrin saturation. VO2max was determined by an indirect test. Results. Statistical difference between the latent iron deficient group versus the iron deficient anemic group was found regarding VO2max (p < 0.001). There were correlations between hemoglobin concentration and VO2max in the latent iron deficient group, as well as in the iron deficient anaemic group (p < 0.05). After two months, there was a significant increase in VO2max in all groups (from 7.0% to 18.2%). Values of VO2max at the end of training period were significantly different (45.98 ? 1.76 vs 42.40 ? 1.22 mL/kg/min; p <0.001) between the experimental and the control group only in female athletes with iron deficiency anemia. After the supplementation, markers of iron status were significantly higher in supplemented groups than in the controls. Conclusion. VO2max was significantly lower in the iron deficient anemic group versus the latent iron deficient group. Iron supplementation during a two-month training period significantly improved body iron status in the iron deficient female athletes with or without anemia, and significantly increased VO2max only in the subjects with iron deficiency anemia.


2017 ◽  
Vol 147 (12) ◽  
pp. 2297-2308 ◽  
Author(s):  
Michael J Wenger ◽  
Laura E Murray-Kolb ◽  
Julie EH Nevins ◽  
Sudha Venkatramanan ◽  
Gregory A Reinhart ◽  
...  

Abstract Background: Iron deficiency and iron deficiency anemia have been shown to have negative effects on aspects of perception, attention, and memory. Objective: The purpose of this investigation was to assess the extent to which increases in dietary iron consumption are related to improvements in behavioral measures of perceptual, attentional, and mnemonic function. Methods: Women were selected from a randomized, double-blind, controlled food-fortification trial involving ad libitum consumption of either a double-fortified salt (DFS) containing 47 mg potassium iodate/kg and 3.3 mg microencapsulated ferrous fumarate/g (1.1 mg elemental Fe/g) or a control iodized salt. Participants' blood iron status (primary outcomes) and cognitive functioning (secondary outcomes) were assessed at baseline and after 10 mo at endline. The study was performed on a tea plantation in the Darjeeling district of India. Participants (n = 126; 66% iron deficient and 49% anemic at baseline) were otherwise healthy women of reproductive age, 18–55 y. Results: Significant improvements were documented for iron status and for perceptual, attentional, and mnemonic function in the DFS group (percentage of variance accounted for: 16.5%) compared with the control group. In addition, the amount of change in perceptual and cognitive performance was significantly (P < 0.05) related to the amount of change in blood iron markers (mean percentage of variance accounted for: 16.0%) and baseline concentrations of blood iron markers (mean percentage of variance accounted for: 25.0%). Overall, there was evidence that the strongest effects of change in iron status were obtained for perceptual and low-level attentional function. Conclusion: DFS produced measurable and significant improvements in the perceptual, attentional, and mnemonic performance of Indian female tea pickers of reproductive age. This trial was registered at clinicaltrials.gov as NCT01032005.


2022 ◽  
Author(s):  
Amanda K. Barks ◽  
Montana M. Beeson ◽  
Timothy C. Hallstrom ◽  
Michael K. Georgieff ◽  
Phu V. Tran

Iron deficiency (ID) during neurodevelopment is associated with lasting cognitive and socioemotional deficits, and increased risk for neuropsychiatric disease throughout the lifespan. These neurophenotypical changes are underlain by gene dysregulation in the brain that outlasts the period of ID; however, the mechanisms by which ID establishes and maintains gene expression changes are incompletely understood. The epigenetic modification 5-hydroxymethylcytosine (5hmC), or DNA hydroxymethylation, is one candidate mechanism because of its dependence on iron-containing TET enzymes. The aim of the present study was to determine the effect of fetal-neonatal ID on regional brain TET activity, Tet expression, and 5hmC in the developing rat hippocampus and cerebellum, and to determine whether changes are reversible with dietary iron treatment. Timed pregnant Sprague-Dawley rats were fed iron deficient diet (ID; 4 mg/kg Fe) from gestational day (G)2 to generate iron deficient anemic (IDA) offspring. Control dams were fed iron sufficient diet (IS; 200 mg/kg Fe). At postnatal day (P)7, a subset of ID-fed litters was randomized to IS diet, generating treated IDA (TIDA) offspring. At P15, hippocampus and cerebellum were isolated for subsequent analysis. TET activity was quantified by ELISA from nuclear proteins. Expression of Tet1, Tet2, and Tet3 was quantified by qPCR from total RNA. Global %5hmC was quantified by ELISA from genomic DNA. ID increased DNA hydroxymethylation (p=0.0105), with a corresponding increase in TET activity (p<0.0001) and Tet3 expression (p<0.0001) in the P15 hippocampus. In contrast, ID reduced TET activity (p=0.0016) in the P15 cerebellum, with minimal effect on DNA hydroxymethylation. Neonatal dietary iron treatment resulted in partial normalization of these changes in both brain regions. These results demonstrate that the TET/DNA hydroxymethylation system is disrupted by developmental ID in a brain region-specific manner. Differential regional disruption of this epigenetic system may contribute to the lasting neural circuit dysfunction and neurobehavioral dysfunction associated with developmental ID.


Endocrinology ◽  
2021 ◽  
Author(s):  
Hannah Roberts ◽  
Andrew G Woodman ◽  
Kelly J Baines ◽  
Mariyan J Jeyarajah ◽  
Stephane L Bourque ◽  
...  

Abstract Iron deficiency occurs when iron demands chronically exceed intake, and is prevalent in pregnant women. Iron deficiency during pregnancy poses major risks for the baby, including fetal growth restriction and long-term health complications. The placenta serves as the interface between a pregnant mother and her baby, and ensures adequate nutrient provisions for the fetus. Thus, maternal iron deficiency may impact fetal growth and development by altering placental function. We used a rat model of diet-induced iron deficiency to investigate changes in placental growth and development. Pregnant Sprague-Dawley rats were fed either a low-iron or iron-replete diet starting two weeks before mating. Compared to controls, both maternal and fetal hemoglobin were reduced in dams fed low-iron diets. Iron deficiency decreased fetal liver and body weight, but not brain, heart or kidney weight. Placental weight was increased in iron deficiency, due primarily to expansion of the placental junctional zone. The stimulatory effect of iron deficiency on junctional zone development was recapitulated in vitro, as exposure of rat trophoblast stem cells to the iron chelator deferoxamine increased differentiation toward junctional zone trophoblast subtypes. Gene expression analysis revealed 464 transcripts changed at least 1.5-fold (P&lt;0.05) in placentas from iron-deficient dams, including altered expression of genes associated with oxygen transport and lipoprotein metabolism. Expression of genes associated with iron homeostasis was unchanged despite differences in levels of their encoded proteins. Our findings reveal robust changes in placentation during maternal iron deficiency, which could contribute to the increased risk of fetal distress in these pregnancies.


2019 ◽  
Vol 15 (1) ◽  
pp. 18-21 ◽  
Author(s):  
Saroj Thapa ◽  
Madhab Lamsal ◽  
Sanjay Kumar Sah ◽  
Rajendra Kumar Chaudhari ◽  
Basanta Gelal ◽  
...  

Background: Iron deficiency is the most common nutritional deficiency in the world. The relation between thyroid hormones and iron status is bidirectional. The aim of this study was to assess iron nutrition status and evaluate its relationship with thyroid hormone profile among children of Eastern Nepal. Methods: A  community based cross-sectional study was conducted in eastern Nepal. A total of 200 school children aged 6-12 years were recruited after taking informed consent from their guardians. Blood samples were collected and assayed for free thyroid hormones (fT3 and fT4), thyroid stimulating hormone (TSH), serum iron, total iron binding capacity (TIBC) concentration and percentage transferrin saturation was calculated. Results: The mean serum iron and TIBC was 74.04 µg/dl and 389.38 µg/dl respectively. The median transferring saturation was 19.21%. The overall prevalence of iron deficiency (Transferrin saturation < 16%) was 34% (n=68). The mean concentration of fT3 and fT4 was 2.87 pg/ml and 1.21 ng/dl respectively, while the median TSH concentration was 3.03 mIU/L. Median TSH concentration in iron deficient group (3.11 µg/dl) and iron sufficient group (2.91 µg/dl) was not significantly different. Among iron deficient children 5.9% had   subclinical hypothyroidism (n=4). Iron status indicators were not significantly correlated with thyroid profile parameters in the study population. Conclusions: The prevalence of iron deficiency is high and iron   deficiency does not significantly alter the thyroid hormone profile in the study region.


Author(s):  
Chintan Upadhyay ◽  
Nisha Upadhyay

Background: Iron deficiency anaemia during pregnancy leads to preterm birth, low birth weight and small-for-gestational age babies and increases incidence of postpartum haemorrhage (PPH) and the reason for the incidence of PPH is higher in India compared with the rest of the world. The objective of this study was to find association between maternal anaemia and neonatal complications and to find long term morbidity and mortality of babies born to anaemic mothers.Methods: It is a prospective study done at Obstetrics and Gynecology Department, Dr. B. R. Ambedkar Medical College and Hospital, Bangalore during October 2009 to October 2011. All subjects were analyzed in full details and haemoglobin estimation done during 1st visit, at 30th week and 36th week of gestation.Results: Study observed moderate anaemia observed in almost 53.0% cases followed by mild (29.5%) and severe (17.5%) respectively. Risk factors present in 58.0% cases and maternal complications in puerperium observed in 14.5% cases. High incidence of adverse foetal outcome in the form of preterm (20%), IUGR (28%), NICU admission (25.5%) and IUD (3%) seen in present study. Study found association between space between pregnancy, LSCS and fetal outcome with severity of anaemia. Ensuring maternal iron sufficiency during gestation is the most cost-effective method of preventing perinatal iron deficiency and related morbidities.Conclusions: Iron supplementation during pregnancy in iron deficient mothers improves iron status during pregnancy and postpartum period, thus providing some protection against iron deficiency in the subsequent pregnancy. Proper antenatal care is the basic requirement for prevention, early detection and treatment of anaemia.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1070-1070
Author(s):  
Brian Sandri ◽  
Gabriele Lubach ◽  
Eric Lock ◽  
Michael Georgieff ◽  
Pamela Kling ◽  
...  

Abstract Objectives To determine whether rapid correction of iron deficiency using intramuscular iron dextran normalizes serum metabolomic changes in a nonhuman primate model of iron deficiency anemia (IDA). Methods Blood was collected from naturally iron-sufficient (IS; n = 10) and IDA (n = 12) male and female infant rhesus monkeys (Macaca mulatta) at 6 months of age. IDA infants were treated with intramuscular injections of iron dextran, 10 mg/weekly for 4–8 weeks. Iron status was reevaluated following treatment using hematological measurements and sera were metabolically profiled using HPLC/MS with isobaric standards for identification and quantification. Results Early-life iron deficiency anemia negatively affects many cellular metabolic processes, including energy production, electron transport, and oxidative degradation of toxins. Slow iron repletion with dietary supplementation restores iron deficient monkeys from a hematological perspective, but the serum metabolomic profile remains differed from monkeys that had been iron sufficient their entire life. Whether rapid iron restoration through intramuscular injections of iron dextran normalizes serum metabolomic profile is not known. A total of 654 metabolites were measured with differences in 53 metabolites identified between IS and IDA monkeys at 6 months (P 0.05). Pathway analyses provided evidence of altered liver function, hypometabolic state, differential essential fatty acid production, irregular inosine and guanosine metabolism, and atypical bile acid production in IDA infants. After treatment, iron-related hematological parameters had recovered, but the formerly IDA infants remained metabolically distinct from the IS infants, with 225 metabolites differentially expressed between the groups. Conclusions As with slow iron repletion, rapid iron repletion does not normalize the altered serum metabolomic profile in rhesus infants with IDA, suggesting the need for iron supplementation in the pre-anemic stage. Funding Sources National Institutes of Health.


Biomolecules ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 60 ◽  
Author(s):  
Tanja Zeller ◽  
Christoph Waldeyer ◽  
Francisco Ojeda ◽  
Renate Schnabel ◽  
Sarina Schäfer ◽  
...  

Acute myocardial infarction remains a leading cause of morbidity and mortality. While iron deficient heart failure patients are at increased risk of future cardiovascular events and see improvement with intravenous supplementation, the clinical relevance of iron deficiency in acute coronary syndrome remains unclear. We aimed to evaluate the prognostic value of iron deficiency in the acute coronary syndrome (ACS). Levels of ferritin, iron, and transferrin were measured at baseline in 836 patients with ACS. A total of 29.1% was categorized as iron deficient. The prevalence of iron deficiency was clearly higher in women (42.8%), and in patients with anemia (42.5%). During a median follow-up of 4.0 years, 111 subjects (13.3%) experienced non-fatal myocardial infarction (MI) and cardiovascular mortality as combined endpoint. Iron deficiency strongly predicted non-fatal MI and cardiovascular mortality with a hazard ratio (HR) of 1.52 (95% confidence interval (CI) 1.03-2.26; p = 0.037) adjusted for age, sex, hypertension, smoking status, diabetes, hyperlipidemia, body-mass-index (BMI) This association remained significant (HR 1.73 (95% CI 1.07–2.81; p = 0.026)) after an additional adjustment for surrogates of cardiac function and heart failure severity (N-terminal pro B-type natriuretic peptide, NT-proBNP), for the size of myocardial necrosis (troponin), and for anemia (hemoglobin). Survival analyses for cardiovascular mortality and MI provided further evidence for the prognostic relevance of iron deficiency (HR 1.50 (95% CI 1.02–2.20)). Our data showed that iron deficiency is strongly associated with adverse outcome in acute coronary syndrome.


Blood ◽  
1976 ◽  
Vol 48 (3) ◽  
pp. 449-455 ◽  
Author(s):  
JD Cook ◽  
CA Finch ◽  
NJ Smith

Abstract The iron status of a population of 1564 subjects living in the northwestern United States was evaluated by measurements of transferrin saturation, red cell protoporphyrin, and serum ferritin. The frequency distribution of these parameters showed no distinct separation between normal and iron-deficient subjects. When only one of these three parameters was abnormal (transferrin saturation below 15%, red cell protoporphyrin above 100 mug/ml packed red blood cells, serum ferritin below 12 ng/ml), the prevalence of anemia was only slightly greater (10.9%) than in the entire sample (8.3%). The prevalence of anemia was increased to 28% in individuals with two or more abnormal parameters, and to 63% when all three parameters were abnormal. As defined by the presence of at least two abnormal parameters, the prevalence of iron deficiency in various populations separated on the basis of age and sex ranged from 3% in adolescent and adult males to 20% in menstruating women. It is concluded that the accuracy of detecting iron deficiency in population surveys can be substantially improved by employing a battery of laboratory measurements of the iron status.


2020 ◽  
Vol 16 (2) ◽  
pp. 220-227 ◽  
Author(s):  
Siti Helmyati ◽  
Endang Sutriswati Rahayu ◽  
Bernadette Josephine Istiti Kandarina ◽  
Mohammad Juffrie

Background: Iron deficiency may inhibit the height increase and weight gain of children. On the other hand, the supplementation of iron causes gut microbiota imbalance which leads to inflammation and diarrhea. The addition of synbiotic fermented milk is expected to have beneficial effects on iron supplementation. This study aimed to determine the effects of iron supplementation only and its administration with synbiotic fermented milk on iron status, body height and weight, and gut microbiota profile of iron deficient elementary school children. Methods: This research was an experimental study with pre and post test conducted on 59 irondeficient children. Subjects were given iron supplementation in syrups (IS group) or given iron supplementation in syrup with fermented milk (containing synbiotic Lactobacillus plantarum Dad 13 and fructo-oligosaccharide) (ISFM group) for 3 months. The body weight and height, hemoglobin and serum ferritin levels, and total number of Lactobacilli, Enterobacteria, Bifidobacteria, and Escherichia coli were measured at the beginning and the end of the study. Results: The body height in the ISFM group increased significantly than that in IS group after the intervention (1.67 vs. 2.42, p<0.05). The hemoglobin and serum ferritin levels in IS and ISFM groups were improved significantly (p<0.05) although the difference between the two groups was not significant (p>0.05). The results showed no significant difference of gut microbiota profile between the IS and ISFM groups (p>0.05). Conclusion: There is no difference on the iron status, height, weight, and gut microbiota profile of iron-deficient primary school children received iron supplementation only or iron supplementation with synbiotic fermented milk.


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