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The SLC39A12 gene encodes the zinc transporter protein ZIP12, which is expressed across many tissues and is highly abundant in the vertebrate nervous system. As a zinc transporter, ZIP12 functions to transport zinc across cellular membranes, including cellular zinc influx across the plasma membrane. Genome-wide association and exome sequencing studies have shown that brain susceptibility-weighted magnetic resonance imaging (MRI) intensity is associated with ZIP12 polymorphisms and rare mutations. ZIP12 is required for neural tube closure and embryonic development in Xenopus tropicalis. Frog embryos depleted of ZIP12 by antisense morpholinos develop an anterior neural tube defect and lack viability. ZIP12 is also necessary for neurite outgrowth and mitochondrial function in mouse neural cells. ZIP12 mRNA is increased in brain regions of schizophrenic patients. Outside of the nervous system, hypoxia induces ZIP12 expression in multiple mammalian species, including humans, which leads to endothelial and smooth muscle thickening in the lung and contributes towards pulmonary hypertension. Other studies have associated ZIP12 with other diseases such as cancer. Given that ZIP12 is highly expressed in the brain and that susceptibility-weighted MRI is associated with brain metal content, ZIP12 may affect neurological diseases and psychiatric illnesses such as Parkinson's disease, Alzheimer's disease, and schizophrenia. Furthermore, the induction of ZIP12 and resultant zinc uptake under pathophysiological conditions may be a critical component of disease pathology, such as in pulmonary hypertension. Drug compounds that bind metals like zinc may be able to treat diseases associated with impaired zinc homeostasis and altered ZIP12 function., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Assessment of zinc status remains a challenge largely because serum/plasma zinc may not accurately reflect an individual's zinc status. The comet assay, a sensitive method capable of detecting intracellular DNA strand breaks, may serve as a functional biomarker of zinc status. We hypothesized that effects of zinc supplementation on intracellular DNA damage could be assessed from samples collected in field studies in Ethiopia using the comet assay. Forty women, from villages where reported consumption of meat was less than once per month and phytate levels were high, received 20 mg zinc as zinc sulfate or placebo daily for 17 days in a randomized placebo-controlled trial. Plasma zinc concentrations were determined by inductively coupled plasma mass spectrometry. Cells from whole blood at the baseline and end point of the study were embedded in agarose, electrophoresed, and stained before being scored by an investigator blinded to the treatments. Although zinc supplementation did not significantly affect plasma zinc, mean (± SEM) comet tail moment measurement of supplemented women decreased from 39.7 ± 2.7 to 30.0 ± 1.8 (P< .005), indicating a decrease in DNA strand breaks in zinc-supplemented individuals. These findings demonstrated that the comet assay could be used as a functional assay to assess the effects of zinc supplementation on DNA integrity in samples collected in a field setting where food sources of bioavailable zinc are limited. Furthermore, the comet assay was sufficiently sensitive to detect changes in zinc status as a result of supplementation despite no significant changes in plasma zinc., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The relation between zinc status and cognitive function was examined in a cross-sectional study in the Sidama area of Southern Ethiopia. Pregnant women >24 weeks of gestation from three adjacent rural villages volunteered to participate. Mean (s.d.) plasma zinc of 99 women was 6.97 (1.07) mumol/l (below the cutoff of 7.6 mumol/l indicative of zinc deficiency at this stage of gestation). The Raven's Coloured Progressive Matrices (CPM) test was administered individually. Scores for the Raven's scale A, which is the simplest scale, ranged from 4 to 10 of a possible 12. Women with plasma zinc <7.6 mumol/l had significantly lower Raven's CPM scale A scores than women with plasma zinc concentrations >7.6 mumol/l. Plasma zinc and maternal age and education predicted 17% of the variation in Raven's CPM scale A scores. We conclude that zinc deficiency is a major factor affecting cognition in these pregnant women.

This study examined relations of blood lead < 10 microg/dL, iron, zinc, and parenting to Head Start children's (N = 112) scores on Peabody Picture Vocabulary Test-III (PPVT-III) and McCarthy Scales of Children's Abilities (MSCA). Venous whole blood and plasma samples were analyzed for lead and zinc by ICP-MS and iron status was assessed by serum transferrin receptors. Hierarchical regressions revealed significant effects of lead on MSCA perceptual scores and iron on PPVT-III and MSCA verbal scores. Children with lead > 2.5 microg/dL had significantly lower MSCA perceptual scores than children < 2.5 microg/dL. Permissive parenting significantly exacerbated negative effects of higher lead or lower iron on children's perceptual or verbal scores, respectively.

Objective: To assess the prevalence of zinc inadequacy based on dietary intakes and plasma zinc concentrations and, simultaneously, the prevalence of inadequate intakes of energy, protein, calcium and iron., Design: A cross-sectional study of a convenience sample of subsistence farming households in Sidama, Southern Ethiopia., Subjects: Dietary intakes were calculated from 1-day weighed food records and 40 repeats from 99 pregnant women in the third trimester using analysed values of major staple foods for zinc, iron, calcium and phytate. The distribution of observed intakes was adjusted for usual intakes and the prevalence of inadequacy estimated using the estimated average requirement (EAR) cutpoint method. Prevalence of inadequacy for zinc, protein and iron intakes were compared with those based on biochemical measures., Results: Prevalence of zinc inadequacy was very high: 99% for US FNB EAR and 100% for IZiNCG EAR compared to 72% based on low plasma zinc concentrations. Corresponding prevalence estimates for iron were much lower: 4% for inadequate intakes based on US FNB EAR vs. 8.7% for iron deficiency anaemia (haemoglobin < 110 g l-1; ferritin < 12 microg l-1) and 32.3% for low storage iron. Prevalence of inadequacy for protein was 100% for adjusted intakes and 91% for serum albumin < 32 g l-1. For calcium, 74% were at risk for inadequate intakes., Conclusion: The high prevalence of inadequate intakes of zinc and protein was reasonably consistent with those based on biochemical measures. Such dietary deficits could be overcome by regular consumption of cellular animal protein. In contrast, both dietary and biochemical measures of iron inadequacy were low.

The etiology of anemia during pregnancy in rural Southern Ethiopia is uncertain. Intakes of animal-source foods are low and infections and bacterial overgrowth probably coexist. We therefore measured the dietary intakes of a convenience sample of Sidama women in late pregnancy who consumed either maize (n = 68) or fermented enset (Enset ventricosum) (n = 31) as their major energy source. Blood samples were analyzed for a complete blood count, vitamin B-12 and folate status, plasma ferritin, retinol, zinc, albumin, and C-reactive protein (CRP). The role of infection and gravida was also examined. Dietary intakes were calculated from 1-d weighed records. No cellular animal products were consumed. Of the women, 29% had anemia, 13% had iron deficiency anemia, 33% had depleted iron stores, and 74 and 27% had low plasma zinc and retinol, respectively. Only 2% had low plasma folate (< 6.8 nmol/L) and 23% had low plasma vitamin B-12 (< 150 pmol/L), even though 62% had elevated plasma methylmalonic acid (MMA) (> 271 nmol/L). None had elevated plasma cystathionine or total homocysteine (tHcys). Women with enset-based diets had higher (P = 0.052) plasma vitamin B-12 concentration and lower (P < 0.05) cell volume, plasma cystathionine, and retinol than women consuming maize-based diets, but mean hemoglobin, plasma ferritin, MMA, tHcys, and folate did not differ. Plasma zinc, followed by CRP (< or = 5 mg/L), gravida (< or = 4), and plasma ferritin (> or = 12 microg/L) status were major positive predictors of hemoglobin. Despite some early functional vitamin B-12 deficiency, there was no macrocytic anemia. Consumption of fermented enset may have increased vitamin B-12 levels in diet and plasma.

Background: Little is yet known about zinc absorption in late pregnancy, and no information on absorption from the total diet is available., Objective: The objective was to measure the fractional absorption of zinc (FAZ) and to estimate the total quantity of absorbed zinc (TAZ) each day during the third trimester of pregnancy in poor rural southern Ethiopian women., Design: The participants (n = 17) were a convenience sample from a larger study population. The third stage of pregnancy was estimated from fundal height by the Bushulo Health Center prenatal outreach program. FAZ was determined with a dual-isotope tracer ratio technique that uses measurements of urine enrichment with zinc stable isotopes administered intravenously and orally, as an extrinsic label, with all meals in 1 d. Total dietary zinc (TDZ) was calculated from weighed diet records and Ethiopian food-composition tables supported by zinc and phytate analyses of major food items for individual meals. Plasma zinc and exchangeable zinc pool size were also estimated., Results: Mean (+/-SD) FAZ was 0.35 +/- 0.11, TDZ was 6.0 +/- 3.2 mg/d, TAZ was 2.1 +/- 1.0 mg/d, phytate intake was 1033 +/- 843 mg/d, plasma zinc was 44.1 +/- 6.0 microg/dL, and the exchangeable zinc pool size was 142 +/- 39 mg. The molar ratio of phytate to zinc was 17:1., Conclusions: Women from a poor rural population who were dependent on a moderately high-phytate diet had low TDZ and low plasma zinc concentrations in the third trimester of pregnancy. TAZ was modestly higher than that predicted but did not meet physiologic requirements.