Doris Kuehnelt1, Karin Engström2, Helena Skröder3, Sabine Kokarnig1, Carina Schlebusch4, Maria Kippler3, Ayman Alhamdow2, Barbro Nermell3, Kevin Francesconi1, Karin Broberg5, Marie Vahter3. 1. Institute of Chemistry, Analytical Chemistry, NAWI Graz, University of Graz, Graz, Austria; 2. Section of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden; 3. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; and. 4. Department of Evolutionary Biology, Evolutionary Biology Center, Uppsala University, Uppsala, Sweden. 5. Section of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; and karin.broberg@ki.se.
Abstract
BACKGROUND: Selenium is an essential element, but its metabolism in humans is not well characterized. A few small studies indicate that the trimethylselenonium ion (TMSe) is a common selenium metabolite in humans. OBJECTIVE: This study aimed to elucidate the human metabolism of selenium to TMSe. DESIGN: Study individuals constituted subsamples of 2 cohorts: 1) pregnant women (n = 228) and their 5-y-old children (n = 205) in rural Bangladesh with poor selenium status [median urinary selenium (U-Se): 6.4 μg/L in mothers, 14 μg/L in children] and 2) women in the Argentinian Andes (n = 83) with adequate selenium status (median U-Se: 24 μg/L). Total U-Se and blood selenium were measured by inductively coupled plasma mass spectrometry (ICPMS), and urinary concentrations of TMSe were measured by high-performance liquid chromatography/vapor generation/ICPMS. A genomewide association study (GWAS) was performed for 1,629,299 (after filtration) single nucleotide polymorphisms (SNPs) in the Bangladeshi women (n = 72) by using Illumina Omni5M, and results were validated by using real-time polymerase chain reaction. RESULTS: TMSe "producers" were prevalent (approximately one-third) among the Bangladeshi women and their children, in whom TMSe constituted ∼10-70% of U-Se, whereas "nonproducers" had, on average, 0.59% TMSe. The TMSe-producing women had, on average, 2-μg U-Se/L higher concentrations than did the nonproducers. In contrast, only 3 of the 83 Andean women were TMSe producers (6-15% TMSe in the urine); the average percentage among the nonproducers was 0.35%. Comparison of the percentage of urinary TMSe in mothers and children indicated a strong genetic influence. The GWAS identified 3 SNPs in the indolethylamine N-methyltransferase gene (INMT) that were strongly associated with percentage of TMSe (P < 0.001, false-discovery rate corrected) in both cohorts. CONCLUSIONS: There are remarkable population and individual variations in the formation of TMSe, which could largely be explained by SNPs in INMT. The TMSe-producing women had higher U-Se concentrations than did nonproducers, but further elucidation of the metabolic pathways of selenium is essential for the understanding of its role in human health. The MINIMat trial was registered at isrctn.org as ISRCTN16581394.
BACKGROUND:Selenium is an essential element, but its metabolism in humans is not well characterized. A few small studies indicate that the trimethylselenonium ion (TMSe) is a common selenium metabolite in humans. OBJECTIVE: This study aimed to elucidate the human metabolism of selenium to TMSe. DESIGN: Study individuals constituted subsamples of 2 cohorts: 1) pregnant women (n = 228) and their 5-y-old children (n = 205) in rural Bangladesh with poor selenium status [median urinary selenium (U-Se): 6.4 μg/L in mothers, 14 μg/L in children] and 2) women in the Argentinian Andes (n = 83) with adequate selenium status (median U-Se: 24 μg/L). Total U-Se and blood selenium were measured by inductively coupled plasma mass spectrometry (ICPMS), and urinary concentrations of TMSe were measured by high-performance liquid chromatography/vapor generation/ICPMS. A genomewide association study (GWAS) was performed for 1,629,299 (after filtration) single nucleotide polymorphisms (SNPs) in the Bangladeshi women (n = 72) by using Illumina Omni5M, and results were validated by using real-time polymerase chain reaction. RESULTS:TMSe "producers" were prevalent (approximately one-third) among the Bangladeshi women and their children, in whom TMSe constituted ∼10-70% of U-Se, whereas "nonproducers" had, on average, 0.59% TMSe. The TMSe-producing women had, on average, 2-μg U-Se/L higher concentrations than did the nonproducers. In contrast, only 3 of the 83 Andean women were TMSe producers (6-15% TMSe in the urine); the average percentage among the nonproducers was 0.35%. Comparison of the percentage of urinary TMSe in mothers and children indicated a strong genetic influence. The GWAS identified 3 SNPs in the indolethylamine N-methyltransferase gene (INMT) that were strongly associated with percentage of TMSe (P < 0.001, false-discovery rate corrected) in both cohorts. CONCLUSIONS: There are remarkable population and individual variations in the formation of TMSe, which could largely be explained by SNPs in INMT. The TMSe-producing women had higher U-Se concentrations than did nonproducers, but further elucidation of the metabolic pathways of selenium is essential for the understanding of its role in human health. The MINIMat trial was registered at isrctn.org as ISRCTN16581394.
Authors: Jiaojiao Li; Chunxiao Sun; Wenwen Cai; Jing Li; Barry P Rosen; Jian Chen Journal: Mutat Res Rev Mutat Res Date: 2021-10-07 Impact factor: 7.015
Authors: Jon G Dean; Tiecheng Liu; Sean Huff; Ben Sheler; Steven A Barker; Rick J Strassman; Michael M Wang; Jimo Borjigin Journal: Sci Rep Date: 2019-06-27 Impact factor: 4.379
Authors: Helena Skröder; Karin Engström; Doris Kuehnelt; Maria Kippler; Kevin Francesconi; Barbro Nermell; Fahmida Tofail; Karin Broberg; Marie Vahter Journal: Environ Health Perspect Date: 2018-02-01 Impact factor: 9.031