1,721,048 research outputs found
Effect of iodine supplementation in Indian pregnant women on maternal and newborn thyroid function and cognitive development
No full textABSTRACT Background: Iodine is a key nutrient in neurodevelopment, and the fetus is entirely dependent on the iodine intake of the mother to fulfill this important requirement for proper brain function. While this is clearly known, it is uncertain if maternal iodine nutrition should be monitored separately against what is in current practice in public health programs to control iodine deficiency. Also, it is unclear whether it is beneficial to supplement pregnant women with iodine in mild-to moderately iodine deficient and also iodine sufficient areas. Finally, the role of thyroid dysfunction in depression during pregnancy is uncertain. Objectives: 1) to determine whether iodine supplementation to pregnant women improves maternal and newborn thyroid function, pregnancy outcome, birth weight, infant growth and cognitive performance; 2) to assess iodine intake and potential determinants of intake, in pregnant women and their children who were sharing all meals; 3) to measure thyroid status during pregnancy and assess potential determinants of maternal thyroid function including iodine status, thyroid autoimmunity, body weight and anemia; 4) to assess the association of maternal depression, and thyroid function during pregnancy. Methods: 1) In a randomized placebo controlled trial (RCT), the MITCH (Maternal Iodine Supplementation and its Effects on Thyroid function and CHild Development) study, pregnant women, gestational age ≤14 weeks, in Bangalore, India, were randomized to receive either a daily supplement of 200 µg oral iodine or placebo from enrolment until delivery. Women were followed through delivery, and then with postnatal follow-up of their infants at 6 weeks, 1 and 2 year. Early neonatal development was assessed using the Neonatal Behavioral Assessment Scale (NBAS) at 6 weeks of age; neurocognitive assessment was done using the Bayley Scales of Infant Development (BSID III) at 1 and 2 years, and BRIEF-P (Behavior Rating Inventory of Executive Function) at 2 years; 2) A cross-sectional study comparing iodine status of pregnant women and their children, who were sharing all meals in Bangalore, India; 3) A cross-sectional study among 334 pregnant women ≤14 weeks of gestation, in Bangalore, India, who were screened for the RCT; 4) Secondary analysis of the longitudinal data on 318 pregnant women in the RCT. Results: 1) In the RCT, there were no significant differences between groups in maternal thyroid function tests or thyroid volume during gestation. The prevalence of thyroid dysfunction or anti-TPO antibodies did not differ significantly during gestation and postpartum. Postpartum, there were no significant differences between the maternal and infant groups in thyroid function, birth outcomes or UIC. Neonates whose mothers received iodine supplementation during pregnancy had better orientation scores at 6 weeks of age and lower scores of inhibition suggesting better executive function at 2 years of age although neurocognitive development on the BSID III were not significantly different between groups; 2) In the pilot study, a) median UIC in pregnant women was 172 µg/L, b) the median UIC was >150 µg/L in all trimesters and c) thyroid size was not significantly different across trimesters; the median UIC in children was 220µg/L, indicating ‘more than adequate’ iodine intake at this age. Median UIC was significantly higher in children than in their mothers (p=0.008). 3) In the cross-sectional study, 21% women were vegetarian, 19% were anemic and 23% were overweight or obese. Iodized salt was used by 98% of women and they were iodine sufficient, median UIC was 184.2 µg/L and all had normal thyroid volume. However, 18% of women had thyroid insufficiency: 3.7% had overt hypothyroidism (83% with positive TPO-Ab), 9.2% had subclinical hypothyroidism and 5.2% had hypothyroxinemia. Women consuming vegetarian diets did not have significantly lower iodine intakes or higher risk of hypothyroidism than those consuming mixed diets, but overweight/obesity and anemia predicted thyroid insufficiency; 4) In the longitudinal study, there was no significant difference in depressive symptoms between the iodine intervention and placebo groups. Women with depressive symptoms had significantly lower serum TSH compared to women without depressive symptoms in the first trimester. Pregnant women with prenatal depressive symptoms had a significantly higher number of medical symptoms. Conclusion: 1) Iodine supplementation in mildly iodine deficient and in iodine sufficient pregnant women was well-accepted and safe and did not increase the risk of excess iodine intake, hyper- or hypothyroidism, or thyroid autoimmunity. Though there were no significant effects of iodine supplementation on neonatal and maternal thyroid function and birth outcomes, there were modest effects on neurocognitive development of children as assessed by executive function of children at 2 years. Thus, additional follow-up of these children for neurocognitive testing at a later age when development and cognitive testing is more reliable would provide valuable add on information; 2) The iodized salt program in Bangalore, India was providing adequate iodine to women throughout pregnancy, at the expense of higher iodine intake in their children, suggesting that the current WHO/UNICEF/ICCIDD cut-off for median UIC in children indicating more-than-adequate intake may need to be reconsidered; 3) Despite iodine sufficiency, many pregnant women had thyroid insufficiency predicted by low hemoglobin and higher BMI. The prevalence of overt hypothyroidism was >5-fold higher than reported in other iodine-sufficient populations of pregnant women, thus, screening of maternal thyroid function should be considered in antenatal care at hospitals in Bangalore, India; 4) Although iodine supplementation did not affect maternal depression, we highlighted the need for systemic screening for prenatal depression during antenatal visits as it is an independent risk factor for later development of clinical depression </p
Unravelling the genetics of iron status in African populations : candidate gene association studies
No full text<strong>Abstract</strong> <strong>Background:</strong> Investigating the manner in which genetic and environmental factors interact to increase susceptibility to iron deficiency, has the potential to impact on strategies to overcome iron deficiency as well as the development of biomarkers to monitor iron status in populations. Single nucleotide polymorphisms or genetic variants that may affect the composition and hence the functionality of proteins involved in iron metabolism have been the subject of recent genetic association studies. However, these investigations have not yet been carried out in African populations that differ genetically from populations of European ancestry and which bear the highest burden of iron deficiency. The overall aim of this thesis was to investigate the genetics of iron status in African populations using a candidate gene approach. <strong>Methods</strong>: In order to evaluate the association between identified TMPRSS6 gene variants and iron status we conducted a systematic review with meta-analyses. We primarily searched the literature using the HuGE Navigator, Pubmed and Scopus databases for primarily genome wide association studies. Fixed effects meta-analysis was used to obtain summary estimates. Associations between reported variants and iron status as well as gene-gene and variant interactions that influence iron status were investigated in a female black South African cohort (n=686; range 32–86 years) which were part of the Prospective Urban and Rural Epidemiology (PURE) study. Concentrations of haemoglobin, serum ferritin, serum transferrin receptor and body iron stores were determined. Thirty SNPs were genotyped and passed all quality criteria. To investigate whether previously identified associations in populations of European ancestry are replicated in populations of African ancestry, we conducted candidate gene association studies. Twenty iron status-associated variants in 628 Kenyans, 609 Tanzanians, 608 South Africans and 228 African Americans were genotyped and associations investigated using haemoglobin and serum ferritin as outcome measures. Finally, we assessed the effect of TNF-α allele variants (TNF‒1031, TNF‒308) on malaria rates, the severity of malaria as indicated by haemoglobin concentrations at the time of presentation with febrile episodes and the association between Plasmodium infection and haemoglobin concentration in symptomless parasite carriers. We used data from a placebo-controlled trial which consisted of 612 Tanzanian children aged 6–60 months. Cox regression models were used in the primary analysis to account for multiple episodes per child. <strong>Results: </strong>In our systematic review we included eleven studies on Caucasian populations, four on Asian populations and one study on an African-American population. Differences in minor allele frequencies (MAF) of 8 TMPRSS6 SNPs (rs855791, rs4820268, rs2111833, rs1421312, rs228921, rs228918, rs228919 and rs575620) across ethnic groups were observed; with the MAF of rs855791 being significantly higher in Asian populations than in Caucasians (0.55 vs 0.42). In the meta-analysis, the A allele of rs855791 was associated with lower haemoglobin and ferritin concentrations in all populations. This allele was also associated with increased serum transferrin receptor and transferrin concentrations. We observed similar associations for the G allele in rs4820268. In general, minor allele frequencies (MAF) from females in the PURE population were lower compared to those of males and females of European ancestry populations in the 1000 Genomes Project. In the TF gene, the SNP rs1799852 was associated with decreased serum ferritin (p=0.01) and body iron concentrations (p=0.03) and increased serum transferrin receptor (sTfR) concentrations (P=0.004), while rs3811647 was associated with transferrin receptor and body iron (both P=0.03) in a U-shaped manner. The chromosome 6 SNP allele combination (AAA) consisting of rs1799964 and rs1800629 both in TNF α and rs2071592 in NFKBIL1 was associated with higher odds for low serum ferritin concentrations (serum ferritin<15µg/L; OR:1.86 (95%-CI, 1.23-2.79)). The chromosome 22 SNP allele combination (GG) consisting of rs228918 and rs228921 in the TMPRSS6 gene was associated with lower odds for increased sTfR concentrations (sTfR>8.3mg/L; OR:0.79 (95%-CI,0.63-0.98). We successfully replicated reported significant associations with lowered haemoglobin concentrations for two loci in TMPRSS6 namely rs2413450 and rs4820268 and with increased haemoglobin concentrations for one locus in TF (rs3811658) when analysing the four populations of African ancestry. When ferritin was considered as an outcome measure, we replicated associations with increased ferritin concentrations in two loci namely, rs228918 in TMPRSS6 and rs1525892 in TF. No other significant associations were determined. Malaria rates were higher in Tanzanian children with the TNF‒1031CC genotype (rs1799964) compared to the AA genotype (crude hazard ratio (HR), 95%CI: 1.41 [1.01‒1.97], adjusted HR 1.31 [0.97‒1.76]y) but were lower in those with the TNF‒308AA genotype (rs1800629) (adjusted HR 0.13 [0.02‒0.63]) compared to those harbouring the wild type homozygous genotype. <strong>Conclusions: </strong>This thesis demonstrates previously observed associations between TMPRSS6 gene variants and haemoglobin concentrations in European ancestry populations are replicated in African populations. Replication of results in other loci previously associated with iron status in European ancestry populations was not achieved. Additionally, minor allele frequencies of single nucleotide polymorphisms associated with iron status are generally higher in European ancestry cohorts compared to those of African ancestry populations. The lack of association of reported variants may indicate that novel loci are responsible for the heritability of iron status in African populations. We have additionally observed that TNF α variants increase malaria severity. Malaria is a major cause of iron deficiency in malaria endemic areas. Our finding emphasizes that to alleviate iron deficiency in malaria endemic areas prevention and treatment of malaria is necessary. This thesis highlights the need to conduct genetic association studies in African populations where iron deficiency is of utmost public health significance. In addition, investigations into the genetics of iron status are bound to contribute towards the development of biomarkers that are useful in the determination of iron status in areas of high inflammation burden.  
Effects of iodine supplementation in mild-to-moderately iodine-deficient pregnant women on thyroid function, pregnancy outcomes and newborn development in Thailand
No full text Background: Iodine deficiency (ID) during pregnancy has been recognized as a major cause of hypothyroidism and adverse health consequences in both mothers and children. Although urinary iodine concentration (UIC) in school-aged children is recommended as an indicator to assess ID in the general population, it may not be a good surrogate for directly assessing iodine status in pregnant women. Iodine supplementation of mildly iodine-deficient pregnant women has been recommended worldwide; however, long-term benefit and safety of iodine supplementation in this group is uncertain. Finally, pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) may negatively affect thyroid function and pregnancy outcomes. Objectives: 1) to measure UIC in pairs of pregnant women and their school-aged children living in the same household; 2) to investigate the effects of iodine supplementation on maternal thyroid function, pregnancy and birth outcomes, and newborn development; 3) to evaluate the association between pre-pregnancy BMI and GWG with thyroid function and pregnancy outcomes. Methods: 1) In a cross-sectional pilot study, UIC was measured in spot urine samples from pairs (n=302) of healthy pregnant mothers and their school-aged children in Bangkok; 2) Arandomized controlled trial was conducted with 200 µg iodine per day or placebo given to mildly ID pregnant Thai women from ndand 3rdtrimester, at delivery and 6-week postpartum. Birth outcomes were collected from hospital records. Neonatal thyroid function, UIC and thyroid volume were measured at delivery and 6 weeks after birth. The Neonatal Behavioral Assessment Scales (NBAS) was used to assess newborn development. Results: 1) In the pilot study, median UIC in the pregnant women was 108 (11–558) µg/L and was lower than UIC in their school-aged children [200 (25–835) µg/L] (P500 µg/L. Maternal thyroid function, thyroid volume and the prevalence of all thyroid dysfunction subtypes did not differ significantly between treatment groups during the study (p>0.05). At 6-week postpartum, the prevalence of postpartum thyroiditis (hyperthyroidism) was significantly lower in the iodine group (3%) as compared to the placebo group (9%) (OR: 95%CI, 0.17: 0.04-0.70). There were no significant differences between newborn groups in thyroid function, thyroid volume, birth characteristics, UIC and NBAS score (p>0.05); 3) Pre-pregnancy BMI was a negative predictor of free thyroxine (fT4) (β=-0.20, P Conclusion: 1) UIC in school-aged children should not be used as a surrogate for monitoring iodine status in pregnancy; 2) iodine supplementation (200 µg/d) in mildly iodine-deficient pregnant Thai women was effective in increasing iodine intakes into the adequate range but had no benefit on antenatal maternal thyroid function or newborn outcomes out to 6 weeks; however, it significantly reduced the risk of maternal postpartum thyroid dysfunction; 3) excess maternal body weight both before and during pregnancy may have adverse impacts on maternal thyroid function as well as birth weight. Therefore, maintaining normal body weight before and throughout pregnancy should be recommended.</p
Zinc biofortification of rice in China: a simulation of zinc intake with different dietary patterns
Full text linkA cross-sectional survey of 2819 adults aged 20 years and above was undertaken in 2002 in Jiangsu Province. Zinc intake was assessed using a consecutive 3-day 24-h dietary recall method. Insufficient and excess intake was determined according to the Chinese Dietary Recommended Intakes. Four distinct dietary patterns were identified namely “traditional”, “macho”, “sweet tooth”, and “healthy”. Intake of zinc from biofortified rice was simulated at an intermediate zinc concentration (2.7 mg/100 g) and a high zinc concentration (3.8 mg/100 g) in rice. Average total zinc intake was 12.0 ± 3.7 mg/day, and insufficiency of zinc intake was present in 15.4%. Simulated zinc intake from biofortified rice with intermediate and high zinc concentration decreased the prevalence of low zinc intake to 6.5% and 4.4%, respectively. The effect was most pronounced in the “traditional” pattern, with only 0.7% of insufficiency of zinc intake remaining in the highest quartile of the pattern. Zinc intake was inversely associated with the “sweet tooth” pattern. Zinc biofortifed rice improves dietary zinc intake and lowers risk for insufficient zinc intake, especially for subjects with a more “traditional” food pattern, but less for subjects with a “sweet tooth” food pattern.Yu Qin, Alida Melse-Boonstra, Baojun Yuan, Xiaoqun Pan, Yue Dai, Minghao Zhou, Rita Wegmueller, Jinkou Zhao, Frans J. Kok and Zumin Shihttp://arxiv.org/abs/arXiv:1205.001
Zinc intake and dietary pattern in Jiangsu Province, China: consequences of nutrition transition
No full text<strong>Background: </strong>Jiangsu Province is an economically booming area in East China, where soil zinc concentrations are low. Nutrition transition to a dietary pattern with more animal source foods may have improved zinc intake in this area. However, such a transition may also have increased the burden of non-communicable diseases (NCDs), such as hypertension and obesity. Investigation of dietary patterns in relation to undernutrition and overnutrition could help to better address both problems. <strong>Objectives: </strong>The first aim of this thesis was to assess zinc status in Jiangsu Province using dietary zinc intake, serum zinc and stunting as indicators, as well to investigate the potential of biofortified rice to improve zinc intake. The second aim was to investigate the association between dietary patterns and high blood pressure, taking obesity into account. <strong>Methods:</strong>Data from the 2002 National Nutrition and Health Survey in Jiangsu Province were used to assess zinc intake in the population aged 4-89 years (n=3,867). Primary school children (n=2,268) were selected from three counties in the Province with relatively low soil zinc for assessment of stunting. Serum zinc was measured among children in the county where stunting was highest (n=297). Thirteen women were recruited in the same county for three test rounds with rice meals (zinc biofortified rice, zinc extruded fortified rice and control rice). Fractional zinc absorption (FAZ) was measured with the use of the double isotope tracer ratio method. Effect of biofortified rice with zinc, at a level of 2.7 and 3.8 mg/100g, on zinc intake was simulated in adults (n=2.819). For adults, four distinct dietary patterns were identified, named “traditional”, “Macho”, “sweet tooth” and “healthy” pattern. Associations were assessed between the four dietary patterns and blood pressure in adults (n=2,518) by using Poisson regression analysis. <strong>Results:</strong>The overall prevalence of insufficient intake of zinc was 22.9%, with a higher prevalence in children (64.6%) and adolescents (64.9%), and in those with low socio-economic status (27.3%). Around 4% of the primary school children were stunted, and the prevalence of zinc deficiency measured by serum and hair zinc was 0.7%, and 15.2%, respectively. Biofortified <sup>70</sup>Zn enriched rice with an intrinsic label was found to have higher fractional zinc absorption (FAZ) than extrinsically labeled fortified extruded rice. However, FAZ could not be accurately quantified because we could not determine the exact amount of isotope infused to subjects due to adhesion of zinc to the vial. When simulating zinc intake by replacing normal rice with zinc biofortified rice with either 2.7 and 3.8 mg/100g of zinc, the prevalence of insufficient zinc intake decreased from 15.4% to 6.5% and 4.4%, respectively. The “traditional” dietary pattern in Jiangsu Province was most strongly associated with high blood pressure (P <sub>for trend</sub> = 0.005). This pattern is characterized primarily by consumption of rice and fresh vegetable; secondary of pork and fish; and lastly of root vegetable and wheat flour, but also by high salt intake. Subjects with overweight and obesity were more likely to have high blood pressure than those with normal weight. <strong>Conclusion: </strong>Children and adolescents had low dietary zinc intake, in Jiangsu Province, where the soil is also deficient in zinc. However, these findings did not match with the low prevalence of stunting and zinc deficiency based on serum zinc concentrations in primary school children from three rural areas of the Province. Zinc appears to be better absorbed from biofortified rice than from control rice or from extruded fortified rice, which needs further investigation. Simulated zinc intake from biofortified rice with zinc at a level of 2.7 mg/kg has the potential to significantly improve zinc intake, especially in the “traditional” dietary pattern. However, this pattern is also related to high blood pressure, which may be due to high salt intake. High blood pressure is also positively and independently related to obesity. Nutrition education is required to improve knowledge and awareness of healthy diets in Jiangsu Province.  
Yellow cassava: efficacy of provitamin A rich cassava on improvement of vitamin A status in Kenyan schoolchildren
No full textBackground: Biofortified yellow cassava has great potential to alleviate vitamin A deficiency in sub-Saharan Africa and can be used as a complementary approach to other interventions. However, direct evidence whether yellow cassava can significantly contribute to the vitamin A intake and status of populations is required. The overall aim of this thesis is to provide proof of principle whether biofortified yellow cassava can improve the vitamin A status of schoolchildren in Kenya. Methods: The research was conducted in Kibwezi district, Eastern Kenya. First the effect of daily consumption of yellow cassava was assessed in 342 primary school children in Kenya in a randomized controlled feeding trial with serum retinol concentration as primary outcome. Furthermore we investigated the sensory and cultural acceptability of yellow cassava in a cross-sectional study (n=140) in three primary schools for children as well as their caretakers. Next we studied the diagnostic performance of several proxy markers to assess vitamin A deficiency in comparison with serum retinol concentration as a field based method to assess vitamin A deficiency (n=375). And last we used the dietary intake data of children in the randomized controlled trial to model the potential contribution of yellow cassava to the nutrient adequacy of micronutrient intake using linear programming. Results: The randomized controlled feeding trial collected complete data for 337 children with a compliance of 100%. Primary analyses (per protocol) showed that serum retinol concentrations in the yellow cassava group, increased with 0.04 μmol/L (95%CI: 0.00‒0.07 μmol/L) compared to the white cassava group and secondary analyses showed that serum β-carotene concentration increased with 524% (448%‒608%). No evidence of effect modification by initial vitamin A status, zinc status, or polymorphisms in the β-carotene monooxygenase gene was found. In the acceptability study 72% of caretakers and children were able to detect a significant difference in taste between white and yellow cassava and indicated to prefer yellow cassava because of its soft texture, sweet taste and attractive color. Serum concentrations of retinol binding protein, transthyretin and C-reactive protein combined showed excellent diagnostic performance in estimating vitamin A deficiency in primary school children, with an area under the curve of 0.98. Adding yellow cassava to the diet as a school lunch improved the nutrient adequacy of the diet of schoolchildren, however, even with the addition of nutrient dense foods such as fish and oil, nutrient adequacy could not be ensured for fat, riboflavin, niacin, folate and vitamin A. Conclusions: Consumption of yellow cassava is acceptable and improves the serum retinol concentrations of primary school children in Kenya. The combination of three proxy markers is a promising approach to measure vitamin A deficiency in a low resource setting. Yellow cassava contributes to a better nutrient adequacy but should be accompanied by additional dietary guidelines and interventions to fill the remaining nutrient gaps
The double burden of malnutrition: obesity and iron deficiency
No full textBackground: The world faces a “double burden” of malnutrition; this is true especially in transition countries like Mexico. The co-existence of obesity and iron deficiency (ID) within a person has been clearly demonstrated in several studies but the mechanisms linking them remain largely unknown. Objectives: To investigate possible mechanisms that link obesity and iron status through the following specific objectives: a) reviewing the existing literature; b) investigating the coexistence of obesity and iron deficiency at the national level in Mexico; c) assessing and comparing iron absorption and blood volume (BV) in healthy, non-anemic women from different body mass index (BMI) categories, and evaluating if ascorbic acid improves iron absorption in overweight (OW) and obese (OB) women; d) evaluating if differences in BV explains reduced iron status in OW/OB women; and e) evaluating whether fat loss in obese subjects decreases inflammation and serum hepcidin and thereby improves iron absorption. Methods: a) A literature review was conducted using Google Scholar and PubMed search engines; b) data from the 1999 Mexican Nutrition Survey, which included 1174 children (aged 5–12 y) and 621 nonpregnant women (aged 18–50 y), was used to assess the relationship between BMI, dietary iron, and dietary factors affecting iron bioavailability, iron status, and inflammation; c & d) healthy, non-anemic Swiss women (n=62) (BMI 18.5-39.9 kg/m2) consumed a stable-isotope labelled wheat-based test meal, without (-AA) and with (+AA) 31.4 mg ascorbic acid. We measured iron absorption, body composition by dual energy X-ray absorptiometry (DXA), blood volume by carbon monoxide (CO)-rebreathing method, iron status, inflammation and serum hepcidin; e) We performed a 6-month, prospective study in OB (BMI, ≥35 Results: a) Obesity-related subclinical inflammation and its effects on hepcidin levels seem to be the most plausible explanation for the link between ID and obesity; b) the risk of iron deficiency in OB women and children was 2-4 times that of normal-weight individuals at similar dietary iron intakes. In addition, we found that C-reactive protein but not iron intake was a strong negative predictor of iron status, independently of BMI (P c) dietary iron absorption was lower in OW/OB versus normal weight subjects (Geometric mean (95%CI): 12.9 (9.7, 16.9)%) vs 19.0 (15.2, 23.5)%, P=0.049). Moreover, the enhancing effect of ascorbic acid on iron absorption in overweight/obese (28%) was only half that in normal weight women (56%); d) OW/OB women presented higher absolute blood volume and lower serum iron compared to the normal weight group. BV (r2=0.22, β=-0.29, P=0.02) was a negative predictor for serum iron when adjusted for body iron stores. We developed an equation to calculate BV in OW and OB women considering weight, height and lean body mass; e) Fat loss lead to a reduction of inflammation (Interleukin-6) and hepcidin concentrations. In iron-deficient subjects (n=17), iron absorption significantly increased after fat loss (Geometric mean (95%CI): 9.7% (6.5-14.6) to 12.4% (7.7-20.1) (P=0.03), while in iron sufficient subjects (n=21), it did not change (Geometric mean (95%CI): 5.9% (4.0-8.6) and 5.6% (3.9-8.2)) (P=0.81)). Conclusion: Increased hepcidin concentrations, along with subclinical inflammation, limits dietary iron absorption in subjects with excessive body fat, especially in iron deficient individuals. Due to a dilutional effect of blood volume, ‘true’ hypoferremia might be overestimated in populations with a high prevalence of obesity when using serum iron as an indicator. OW/OB individuals may require: higher dietary iron intake combined with iron absorption enhancers to keep their iron status in balance; and a reduction of the obesity-related inflammatory process in order to ensure adequate iron absorption.</p
The effects of multi-nutrient fortified dairy-based formulas on growth, anaemia, and micronutrient status in Nigerian late preterm infants and moderately malnourished toddlers
No full textUnravelling the genetics of iron status in African populations : candidate gene association studies
No full textAbstract Background: Investigating the manner in which genetic and environmental factors interact to increase susceptibility to iron deficiency, has the potential to impact on strategies to overcome iron deficiency as well as the development of biomarkers to monitor iron status in populations. Single nucleotide polymorphisms or genetic variants that may affect the composition and hence the functionality of proteins involved in iron metabolism have been the subject of recent genetic association studies. However, these investigations have not yet been carried out in African populations that differ genetically from populations of European ancestry and which bear the highest burden of iron deficiency. The overall aim of this thesis was to investigate the genetics of iron status in African populations using a candidate gene approach. Methods: In order to evaluate the association between identified TMPRSS6 gene variants and iron status we conducted a systematic review with meta-analyses. We primarily searched the literature using the HuGE Navigator, Pubmed and Scopus databases for primarily genome wide association studies. Fixed effects meta-analysis was used to obtain summary estimates. Associations between reported variants and iron status as well as gene-gene and variant interactions that influence iron status were investigated in a female black South African cohort (n=686; range 32–86 years) which were part of the Prospective Urban and Rural Epidemiology (PURE) study. Concentrations of haemoglobin, serum ferritin, serum transferrin receptor and body iron stores were determined. Thirty SNPs were genotyped and passed all quality criteria. To investigate whether previously identified associations in populations of European ancestry are replicated in populations of African ancestry, we conducted candidate gene association studies. Twenty iron status-associated variants in 628 Kenyans, 609 Tanzanians, 608 South Africans and 228 African Americans were genotyped and associations investigated using haemoglobin and serum ferritin as outcome measures. Finally, we assessed the effect of TNF-α allele variants (TNF‒1031, TNF‒308) on malaria rates, the severity of malaria as indicated by haemoglobin concentrations at the time of presentation with febrile episodes and the association between Plasmodium infection and haemoglobin concentration in symptomless parasite carriers. We used data from a placebo-controlled trial which consisted of 612 Tanzanian children aged 6–60 months. Cox regression models were used in the primary analysis to account for multiple episodes per child. Results: In our systematic review we included eleven studies on Caucasian populations, four on Asian populations and one study on an African-American population. Differences in minor allele frequencies (MAF) of 8 TMPRSS6 SNPs (rs855791, rs4820268, rs2111833, rs1421312, rs228921, rs228918, rs228919 and rs575620) across ethnic groups were observed; with the MAF of rs855791 being significantly higher in Asian populations than in Caucasians (0.55 vs 0.42). In the meta-analysis, the A allele of rs855791 was associated with lower haemoglobin and ferritin concentrations in all populations. This allele was also associated with increased serum transferrin receptor and transferrin concentrations. We observed similar associations for the G allele in rs4820268. In general, minor allele frequencies (MAF) from females in the PURE population were lower compared to those of males and females of European ancestry populations in the 1000 Genomes Project. In the TF gene, the SNP rs1799852 was associated with decreased serum ferritin (p=0.01) and body iron concentrations (p=0.03) and increased serum transferrin receptor (sTfR) concentrations (P=0.004), while rs3811647 was associated with transferrin receptor and body iron (both P=0.03) in a U-shaped manner. The chromosome 6 SNP allele combination (AAA) consisting of rs1799964 and rs1800629 both in TNF α and rs2071592 in NFKBIL1 was associated with higher odds for low serum ferritin concentrations (serum ferritin8.3mg/L; OR:0.79 (95%-CI,0.63-0.98). We successfully replicated reported significant associations with lowered haemoglobin concentrations for two loci in TMPRSS6 namely rs2413450 and rs4820268 and with increased haemoglobin concentrations for one locus in TF (rs3811658) when analysing the four populations of African ancestry. When ferritin was considered as an outcome measure, we replicated associations with increased ferritin concentrations in two loci namely, rs228918 in TMPRSS6 and rs1525892 in TF. No other significant associations were determined. Malaria rates were higher in Tanzanian children with the TNF‒1031CC genotype (rs1799964) compared to the AA genotype (crude hazard ratio (HR), 95%CI: 1.41 [1.01‒1.97], adjusted HR 1.31 [0.97‒1.76]y) but were lower in those with the TNF‒308AA genotype (rs1800629) (adjusted HR 0.13 [0.02‒0.63]) compared to those harbouring the wild type homozygous genotype. Conclusions: This thesis demonstrates previously observed associations between TMPRSS6 gene variants and haemoglobin concentrations in European ancestry populations are replicated in African populations. Replication of results in other loci previously associated with iron status in European ancestry populations was not achieved. Additionally, minor allele frequencies of single nucleotide polymorphisms associated with iron status are generally higher in European ancestry cohorts compared to those of African ancestry populations. The lack of association of reported variants may indicate that novel loci are responsible for the heritability of iron status in African populations. We have additionally observed that TNF α variants increase malaria severity. Malaria is a major cause of iron deficiency in malaria endemic areas. Our finding emphasizes that to alleviate iron deficiency in malaria endemic areas prevention and treatment of malaria is necessary. This thesis highlights the need to conduct genetic association studies in African populations where iron deficiency is of utmost public health significance. In addition, investigations into the genetics of iron status are bound to contribute towards the development of biomarkers that are useful in the determination of iron status in areas of high inflammation burden
Anemia in relation to body mass index and waist circumference among Chinese women
Full text linkExtent: 3 p.BACKGROUND: This study aimed to investigate the relationship of anemia and body mass index among adult women in Jiangsu Province, China. Data were collected in a sub-national cross-sectional survey, and 1,537 women aged 20 years and above were included in the analyses. Subjects were classified by body mass index (BMI) categories as underweight, normal weight, overweight and obese according to the Chinese standard. Central obesity was defined as a waist circumference ≥ 80 cm. Anemia was defined as hemoglobin concentration < 12 g/dl. Prevalence ratios (PRs) of the relationship between anemia and BMI or waist circumference were calculated using Poisson regression. FINDINGS: Overall, 31.1% of the Chinese women were anemic. The prevalence of overweight, obesity and central obesity was 34.2%, 5.8% and 36.2%, respectively. The obese group had the highest concentrations of haemoglobin compared with other BMI groups. After adjustment for confounders, overweight and obese women had a lower PR for anemia (PR: 0.72, 95% CI: 0.62-0.89; PR: 0.59, 95% CI: 0.43-0.79). Central obesity was inversely associated with anemia. CONCLUSION: In this Chinese population, women with overweight/obesity or central obesity were less likely to be anemic as compared to normal weight women. No measures are required currently to target anemia specifically for overweight and obese people in China.Yu Qin, Alida Melse-Boonstra, Xiaoqun Pan, Baojun Yuan, Yue Dai, Jinkou Zhao, Michael B. Zimmermann, Frans J. Kok, Minghao Zhou and Zumin Sh
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