The &lt;i&gt;TMPRSS6&lt;/i&gt; variant (SNP rs855791) affects iron metabolism and oral iron absorption – a stable iron isotope study in Taiwanese women

Buerkli, Simone; Pei, Sung‐Nan; Hsiao, Shu-Chen; Lee, Chien-Te; Zeder, Christophe; Zimmermann, Michael; Moretti, Diego

doi:10.3324/haematol.2020.264556

Cited by 9 publications

(13 citation statements)

References 39 publications

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“…A similar finding of the risk allele among Pakistani women was reported in a recent study by Buerkli et al [68]. In a study of iron absorption in Taiwanese women utilising stable iron isotopes, the T allele was linked to a higher risk of developing iron deficiency, with serum iron and transferrin saturation being lower in the TT version of rs855791 [68]. This revealed that women with the TMPRSS6 rs855791 (2321 C > T) polymorphism have impaired iron homeostasis, which affects oral iron absorption and may increase the risk of IDA.…”

Section: Risk Allele Of Tmprss6 Gene Polymorphismsupporting

confidence: 89%

“…In contrast, a study of reproductive-age Pakistani women found that the rs855791 T allele is linked to the incidence of IDA [70]. A similar finding of the risk allele among Pakistani women was reported in a recent study by Buerkli et al [68]. In a study of iron absorption in Taiwanese women utilising stable iron isotopes, the T allele was linked to a higher risk of developing iron deficiency, with serum iron and transferrin saturation being lower in the TT version of rs855791 [68].…”

Section: Risk Allele Of Tmprss6 Gene Polymorphismsupporting

confidence: 68%

“…It is unclear whether the TMPRSS6 SNP (rs855791) is associated with IDA in menstruating women because some do not develop IDA while others do. Among the Taiwanese IDA women, heterozygous (C > T) rs855791 increases the risk for IDA [50,68]. Despite that, the homozygous (CC) of rs855791 has a protective effect against IDA, particularly in heavy menstruating women.…”

Section: Identification Of Snps In the Tmprss6 Genementioning

confidence: 99%

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TMPRSS6 gene polymorphisms associated with iron deficiency anaemia among global population

Atan

Saman

Kamsani

et al. 2022

Egypt J Med Hum Genet

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Iron deficiency anaemia (IDA) has been recognised as a common global health problem that affects more than 1.2 billion people worldwide, particularly in high-risk individuals such as young children, pre-menopausal women, and pregnant women. In most cases, IDA arises due to the prolonged effect of iron deficiency (ID). On the other hand, it has been estimated that iron deficiency without anaemia is more frequent nowadays. Apart from the lack of nutrients, infections and inflammatory diseases, genetic factors can also be another factor that drives iron instability in the blood, leading to IDA. Previous studies, including genome-wide association studies, have identified multiple transmembrane protease serine 6 (TMPRSS6) genetic variants associated with different iron parameters, especially variants contributing to an increase in hepcidin level, low blood, and iron status. Despite multiple studies on TMPRSS6 gene polymorphisms, fewer studies are reported among the Asian population. Thus, further association studies of TMPRSS6 genetic polymorphisms between ID and IDA are warranted among the Asian population. This review provides a comprehensive summary of the causative TMPRSS6 genetic variants and their roles associated with iron deficiency among the global population.

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Section: Risk Allele Of Tmprss6 Gene Polymorphismsupporting

confidence: 89%

Section: Risk Allele Of Tmprss6 Gene Polymorphismsupporting

confidence: 68%

Section: Identification Of Snps In the Tmprss6 Genementioning

confidence: 99%

See 1 more Smart Citation

TMPRSS6 gene polymorphisms associated with iron deficiency anaemia among global population

Atan

Saman

Kamsani

et al. 2022

Egypt J Med Hum Genet

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“…TMPRSS6 polymorphisms are more frequent than germline TMPRSS6 mutations, and common TMPRSS6 variants are associated with erythrocyte traits, including haemoglobin concentration (Hb), haematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and red blood cell (RBC) count [ 44 , 45 ]. Additionally, TMPRSS6 polymorphisms in iron deficiency anaemia are partially responsive to oral iron treatment [ 46 , 47 ]. A 3-tier classification system for variants of the TMPRSS6 gene has been proposed to better understand and define the IRIDA spectrum [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

The global prevalence and ethnic heterogeneity of iron-refractory iron deficiency anaemia

Fan

Zhao

Sun

2023

Orphanet J Rare Dis

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Background Iron-refractory iron deficiency anaemia (IRIDA) is an autosomal recessive iron deficiency anaemia caused by mutations in the TMPRSS6 gene. Iron deficiency anaemia is common, whereas IRIDA is rare. The prevalence of IRIDA is unclear. This study aimed to estimate the carrier frequency and genetic prevalence of IRIDA using Genome Aggregation Database (gnomAD) data. Methods The pathogenicity of TMPRSS6 variants was interpreted according to the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) standards and guidelines. The minor allele frequency (MAF) of TMPRSS6 gene disease-causing variants in 141,456 unique individuals was examined to estimate the global prevalence of IRIDA in seven ethnicities: African/African American (afr), American Admixed/Latino (amr), Ashkenazi Jewish (asj), East Asian (eas), Finnish (fin), Non-Finnish European (nfe) and South Asian (sas). The global and population-specific carrier frequencies and genetic prevalence of IRIDA were calculated using the Hardy–Weinberg equation. Results In total, 86 pathogenic/likely pathogenic variants (PV/LPV) were identified according to ACMG/AMP guideline. The global carrier frequency and genetic prevalence of IRIDA were 2.02 per thousand and 1.02 per million, respectively. Conclusions The prevalence of IRIDA is greater than previous estimates.

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“…This finding is similar to our results on this SNP. Also, in an iron absorption study in Taiwanese women using stable iron isotopes, Buerkli et al ( 31 ) reported that the TMPRSS6 rs855791 alters iron absorption, and that the carriers of the C alleles absorbed iron better than T allele carriers. Our study was short (5 h) and we did not use stable isotopes.…”

Section: Discussionmentioning

confidence: 99%

Common Variants in the TMPRSS6 Gene Alter Hepcidin but not Plasma Iron in Response to Oral Iron in Healthy Gambian Adults: A Recall-by-Genotype Study

Jallow¹,

Campino²,

Saidykhan³

et al. 2021

Current Developments in Nutrition

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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.

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The <i>TMPRSS6</i> variant (SNP rs855791) affects iron metabolism and oral iron absorption – a stable iron isotope study in Taiwanese women

Cited by 9 publications

References 39 publications

TMPRSS6 gene polymorphisms associated with iron deficiency anaemia among global population

TMPRSS6 gene polymorphisms associated with iron deficiency anaemia among global population

The global prevalence and ethnic heterogeneity of iron-refractory iron deficiency anaemia

Common Variants in the TMPRSS6 Gene Alter Hepcidin but not Plasma Iron in Response to Oral Iron in Healthy Gambian Adults: A Recall-by-Genotype Study

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