Selenium metabolism to the trimethylselenonium ion (TMSe) varies markedly because of polymorphisms in the indolethylamine N-methyltransferase gene
2015 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 102, no 6, 1406-1415 p.Article in journal (Refereed) PublishedText
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 mu g/L in mothers, 14 mu g/L in children] and 2) women in the Argentinian Andes (n = 83) with adequate selenium status (median U-Se: 24 mu g/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 similar to 10-70% of U-Se, whereas "nonproducers" had, on average, 0.59% TMSe. The TMSe-producing women had, on average, 2-mu g 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.
Place, publisher, year, edition, pages
2015. Vol. 102, no 6, 1406-1415 p.
selenium, methylation, essential, human urine, population differences, excretion, metabolite, child, rs6970396, rs1061644, rs4270015
Nutrition and Dietetics
IdentifiersURN: urn:nbn:se:uu:diva-270932ISI: 000365717300015PubMedID: 26537946OAI: oai:DiVA.org:uu-270932DiVA: diva2:890943
FunderSwedish Research CouncilSwedish Research Council FormasSida - Swedish International Development Cooperation AgencyThe Karolinska Institutet's Research FoundationForte, Swedish Research Council for Health, Working Life and Welfare
De två första författarna bidrog i lika stor utsträckning till artikeln2016-01-052016-01-052016-08-09Bibliographically approved