scholarly journals The Association of TMPRSS6 Gene Polymorphism and Iron Intake with Iron Status among Under-Two-Year-Old Children in Lombok, Indonesia

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 878
Author(s):  
Dewi Shinta ◽  
Chris Adhiyanto ◽  
Min Htet ◽  
Umi Fahmida ◽  
Keyword(s):  
Iron Status ◽  
Association Studies ◽  
Iron Concentration ◽  
Hemoglobin Concentration ◽  
Minor Allele ◽  
Genome Wide Association Studies ◽  
Iron Intake ◽  
Genetic Characteristics ◽  
Genome Wide ◽  
Hb Concentration

Multiple common variants in transmembrane protease serine 6 (TMPRSS6) were associated with the plasma iron concentration in genome-wide association studies, but their effect in young children where anemia and iron deficiency (ID) were prevalent has not been reported, particularly taking account of iron intake. This study aims to investigate whether TMPRSS6 SNPs (rs855791 and rs4820268) and iron intake are associated with a low iron and hemoglobin concentration in under-two-year-old children. The study analyzed the baseline of a randomized trial (NUPICO, ClinicalTrials.gov NCT01504633) in East Lombok, Indonesia. Children aged 6–17 months (n = 121) were included in this study. The multiple linear regressions showed that TMPRSS6 decreased serum ferritin (SF) by 4.50 g/L per copy minor allele (A) of rs855791 (p = 0.08) and by 5.00 μg/L per copy minor allele (G) of rs4820268 (p = 0.044). There were no associations between rs855791 and rs4820268 with soluble transferrin receptor (sTfR) and hemoglobin (Hb) concentration (rs855791; p = 0.38 and p = 0.13, rs4820268; p = 0.17 and p = 0.33). The finding suggests the need for further studies to explore whether the nutrient recommendation for iron should be based on genetic characteristics, particularly for children who have mutation in TMPRSS6.

scholarly journals Comparison of the Performance of Two Commercial Genome-Wide Association Study Genotyping Platforms in Han Chinese Samples

2013 ◽  
Vol 3 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Lei Jiang ◽  
Dana Willner ◽  
Patrick Danoy ◽  
Huji Xu ◽  
Matthew A Brown
Keyword(s):  
Allele Frequency ◽  
Minor Allele Frequency ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Han Chinese ◽  
Minor Allele ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Genome Wide

Abstract Most genome-wide association studies to date have been performed in populations of European descent, but there is increasing interest in expanding these studies to other populations. The performance of genotyping chips in Asian populations is not well established. Therefore, we sought to test the performance of widely used fixed-marker, genome-wide association studies chips in the Han Chinese population. Non-HapMap Chinese samples (n = 396) were genotyped using the Illumina OmniExpress and Affymetrix 6.0 platforms, whereas a subset also were genotyped using the Immunochip. Genotyped markers from the Affymetrix 6.0 and Illumina OmniExpress were used for full genome imputation based on the HapMap 2 JPT+CHB (Japanese from Tokyo, Japan and Chinese from Beijing, China) reference panel. The concordance between markers genotypes for the three platforms was very high whether directly genotyped or genotyped and imputed single nucleotide polymorphisms (SNPs; >99.8% for directly genotyped and >99.5% for genotyped and imputed SNPs, respectively) were compared. The OmniExpress chip data enabled more SNPs to be imputed, particularly SNPs with minor allele frequency >5%. The OmniExpress chip achieved better coverage of HapMap SNPs than the Affymetrix 6.0 chip (73.6% vs. 65.9%, respectively, for minor allele frequency >5%). The Affymetrix 6.0 and Illumina OmniExpress chip have similar genotyping accuracy and provide similar accuracy of imputed SNPs. The OmniExpress chip however provides better coverage of Asian HapMap SNPs, although its coverage of HapMap SNPs is moderate.

scholarly journals Genome-wide meta-analysis of iron status biomarkers and the effect of iron on all-cause mortality in HUNT

2021 ◽  
Author(s):  
Marta R Moksnes ◽  
Ailin Falkmo Hansen ◽  
Sarah E Graham ◽  
Sarah A Gagliano Taliun ◽  
Kuan-Han Wu ◽  
...  
Keyword(s):  
Serum Iron ◽  
Iron Status ◽  
Association Studies ◽  
Meta Analysis ◽  
Harmful Effect ◽  
Transferrin Saturation ◽  
Risk Scores ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
All Cause Mortality

AbstractIron is essential for many biological processes, but iron levels must be tightly regulated to avoid harmful effects of both iron deficiency and overload. Here, we perform genome-wide association studies on four iron related biomarkers (serum iron, serum ferritin, transferrin saturation, total iron binding capacity) in the Trøndelag Health Study (HUNT), the Michigan Genomics Initiative (MGI) and the SardiNIA study, followed by their meta-analysis with publicly available summary statistics, analyzing up to 257 953 individuals. We identify 127 genetic loci associated with iron traits. Among 19 novel protein-altering variants, we observe a rare missense variant (rs367731784) in HUNT, which suggests a role for DNAJC13 in transferrin recycling. We further validate the latest genetic risk scores for each biomarker in HUNT (6% variance in serum iron explained) and present linear and non-linear Mendelian randomization analyses of the traits on all-cause mortality. We find evidence of a harmful effect of increased serum iron and transferrin saturation in linear analyses that estimate population-averaged effects. However, there was weak evidence of a protective effect of increasing serum iron at the very low end of its distribution. Our findings contribute to our understanding of the genes affecting iron status and its consequences on human health.

scholarly journals Common variants in the transmembrane protease serine 6 (TMPRSS6) gene alter hepcidin but not plasma iron in response to oral iron in healthy Gambian adults: a recall-by-genotype study

2021 ◽  
Author(s):  
Momodou W Jallow ◽  
Susana Campino ◽  
Alasana Saidykhan ◽  
Andrew M Prentice ◽  
Carla Cerami
Keyword(s):  
Oral Dose ◽  
Iron Status ◽  
Association Studies ◽  
Oral Iron ◽  
Genome Wide Association Studies ◽  
Genetic Determinants ◽  
Plasma Iron ◽  
Risk Alleles ◽  
Genome Wide ◽  
Iron Parameters

Abstract Background The role of genetic determinants in mediating iron status in Africans is not fully understood. Genome-wide association studies in non-African populations have revealed genetic variants in the TMPRSS6 gene that are associated with the risk of anemia. Objectives To investigated the effects of risk alleles for low iron status from TMPRSS6 rs2235321, rs855791 and rs4820268, on responses to oral iron in healthy Gambian adults. Methods Using a recall-by-genotype design, participants were selected from a pre-genotype cohort of 3000 individuals in the Keneba Biobank (MRCG at LSHTM). Participants were invited to participate in the study based on nine genotype combinations obtained from three TMPRSS6 SNPs (rs2235321, rs855791 and rs4820268). The participants fasted overnight and then ingested a single oral dose of ferrous sulfate (130 mg elemental iron). Blood samples were collected prior to iron ingestion and at 2 and 5 hours after the oral iron dose. The effects of genotype on hepcidin and plasma iron parameters were assessed. Results A total of 251 individuals were enrolled. Homozygous carriers of the major TMPRSS6 alleles at each of the SNPs had higher plasma hepcidin at baseline (rs2235321: GG vs AA 9.50 vs 6.60ng/ml,  p = 0.035; rs855791: GG vs AG = 9.50 vs 4.96ng/mL,  p = 0.015; rs4820268: AA vs GG = 9.50 vs 3.27ng/mL,  p = 0.002) and at subsequent timepoints. There were no differences in delta plasma iron (a proxy for iron absorption) between genotypes. In most subjects, hepcidin levels increased following iron ingestion (overall group mean = 4.98 ± 0.98ng/ml at 5h,  p < 0.001),  but double heterozygotes at rs2235321 and rs855791 showed no increase (0.36 ± 0.40ng/ml at 5h,  p = 0.667). Conclusions This study revealed that common TMPRSS6 variants influence hepcidin concentrations, but not iron status indicators either at baseline or following a large oral dose of iron. These results suggest that genetic variations in the TMPRSS6 gene are unlikely to be important contributors to variations in iron status in Africans. This study was registered at ClinicalTrials.gov # NCT03341338.

scholarly journals Iron Biofortification of Staple Crops: Lessons and Challenges in Plant Genetics

2019 ◽  
Vol 60 (7) ◽  
pp. 1447-1456 ◽  
Author(s):  
James M Connorton ◽  
Janneke Balk
Keyword(s):  
Association Studies ◽  
Total Concentration ◽  
Iron Concentration ◽  
World Population ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Global Health Issue ◽  
Iron And Zinc ◽  
Staple Crops ◽  
Zinc Levels

Abstract Plants are the ultimate source of iron in our diet, either directly as staple crops and vegetables or indirectly via animal fodder. Increasing the iron concentration of edible parts of plants, known as biofortification, is seen as a sustainable approach to alleviate iron deficiency which is a major global health issue. Advances in sequencing and gene technology are accelerating both forward and reverse genetic approaches. In this review, we summarize recent progress in iron biofortification using conventional plant breeding or transgenics. Interestingly, some of the gene targets already used for transgenic approaches are also identified as genetic factors for high iron in genome-wide association studies. Several quantitative trait loci and transgenes increase both iron and zinc, due to overlap in transporters and chelators for these two mineral micronutrients. Research efforts are predominantly aimed at increasing the total concentration of iron but enhancing its bioavailability is also addressed. In particular, increased biosynthesis of the metal chelator nicotianamine increases iron and zinc levels and improves bioavailability. The achievements to date are very promising in being able to provide sufficient iron in diets with less reliance on meat to feed a growing world population.

scholarly journals Association of common TMPRSS6 and TF gene variants with hepcidin and iron status in healthy rural Gambians

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Momodou W. Jallow ◽  
Susana Campino ◽  
Andrew M. Prentice ◽  
Carla Cerami
Keyword(s):  
Binding Capacity ◽  
Iron Status ◽  
Association Studies ◽  
Transferrin Saturation ◽  
Genome Wide Association Studies ◽  
Iron Binding ◽  
Functional Studies ◽  
Genome Wide ◽  
Tf Gene ◽  
Iron Binding Capacity

AbstractGenome-wide association studies in Europeans and Asians have identified numerous variants in the transmembrane protease serine 6 (TMPRSS6) and transferrin (TF) genes that are associated with changes in iron status. We sought to investigate the effects of common TMPRSS6 and TF gene SNPs on iron status indicators in a cohort of healthy Africans from rural Gambia. We measured iron biomarkers and haematology traits on individuals participating in the Keneba Biobank with genotype data on TMPRSS6 (rs2235321, rs855791, rs4820268, rs2235324, rs2413450 and rs5756506) and TF (rs3811647 and rs1799852), n = 1316. After controlling for inflammation, age and sex, we analysed the effects of carrying either single or multiple iron-lowering alleles on iron status. TMPRSS6 rs2235321 significantly affected plasma hepcidin concentrations (AA genotypes having lower hepcidin levels; F ratio 3.7, P = 0.014) with greater impact in individuals with low haemoglobin or ferritin. No other TMPRSS6 variant affected hepcidin. None of the TMPRSS6 variants nor a TMPRSS6 allele risk score affected other iron biomarkers or haematological traits. TF rs3811647 AA carriers had 21% higher transferrin (F ratio 16.0, P < 0.0001), 24% higher unsaturated iron-binding capacity (F ratio 12.8, P < 0.0001) and 25% lower transferrin saturation (F ratio 4.3, P < 0.0001) compared to GG carriers. TF rs3811647 was strongly associated with transferrin, unsaturated iron-binding capacity (UIBC) and transferrin saturation (TSAT) with a single allele effect of 8–12%. There was no association between either TF SNP and any haematological traits or iron biomarkers. We identified meaningful associations between TMPRSS6 rs2235321 and hepcidin and replicated the previous findings on the effects of TF rs3811647 on transferrin and iron binding capacity. However, the effects are subtle and contribute little to population variance. Further genetic and functional studies, including polymorphisms frequent in Africa populations, are needed to identify markers for genetically stratified approaches to prevention or treatment of iron deficiency anaemia.

scholarly journals Genome-Wide Polygenic Risk Score for Predicting High Risk Glaucoma Individuals of Han Chinese Ancestry

2021 ◽  
Vol 11 (11) ◽  
pp. 1169
Author(s):  
Yu-Jer Hsiao ◽  
Hao-Kai Chuang ◽  
Sheng-Chu Chi ◽  
Yung-Yu Wang ◽  
Pin-Hsuan Chiang ◽  
...  
Keyword(s):  
Risk Score ◽  
Molecular Mechanisms ◽  
Association Studies ◽  
Han Chinese ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Genetic Characteristics ◽  
Polygenic Risk ◽  
Genome Wide ◽  
Increased Risk

Glaucoma is a progressive and irreversible blindness-causing disease. However, the underlying genetic factors and molecular mechanisms remain poorly understood. Previous genome-wide association studies (GWAS) have made tremendous progress on the SNP-based disease association and characterization. However, most of them were conducted for Europeans. Since differential genetic characteristics among ethnic groups were evident in glaucoma, it is worthwhile to complete its genetic landscape from the larger cohorts of Asian individuals. Here, we present a GWAS based on the Taiwan Biobank. Among 1013 glaucoma patients and 36,562 controls, we identified a total of 138 independent glaucoma-associated SNPs at the significance level of p < 1 × 10−5. After clumping genetically linked SNPs (LD clumping), 134 independent SNPs with p < 10−4 were recruited to construct a Polygenic Risk Score (PRS). The model achieved an area under the receiver operating characteristic curve (AUC) of 0.8387 (95% CI = [0.8269–0.8506]), and those within the top PRS quantile had a 45.48-fold increased risk of glaucoma compared with those within the lowest quantile. The PRS model was validated with an independent cohort that achieved an AUC of 0.7283, thereby showing the effectiveness of our polygenic risk score in predicting individuals in the Han Chinese population with higher glaucoma risks.

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