Characterization of zinc amino acid complexes for zinc delivery in vitro using Caco-2 cells and enterocytes from hiPSC

Zn is essential for growth and development. The bioavailability of Zn is affected by several factors such as other food components. It is therefore of interest, to understand uptake mechanisms of Zn delivering compounds to identify ways to bypass the inhibitory effects of these factors. Here, we studied the effect of Zn amino acid conjugates (ZnAAs) on the bioavailabilty of Zn. We used Caco-2 cells and enterocytes differentiated from human induced pluripotent stem cells from a control and Acroder- matitis enteropathica (AE) patient, and performed fluorescence based assays, protein biochemistry and atomic absorption spectrometry to characterize cellular uptake and absorption of ZnAAs. The results show that ZnAAs are taken up by AA transporters, leading to an intracellular enrichment of Zn mostly uninhibited by Zn uptake antagonists. Enterocytes from AE patients were unable to gain significant Zn through exposure to ZnCl2 but did not show differences with respect to ZnAAs. We conclude that ZnAAs may possess an advantage over classical Zn supplements such as Zn salts, as they may be able to increase bioavailability of Zn, and may be more efficient in patients with AE

SNPs showing strong evidence for functional importance based on bioinformatics.

<p>SNPs showing strong evidence for functional importance based on bioinformatics.</p

Comparison of <i>P</i>-values for GWAS-identified variants (index SNPs) vs. variants with the smallest <i>P</i>-values (top SNPs) in 31 regions.

<p>The height of each bar reflects the–log10 <i>P</i>-value of each SNP in our study population. A grey bar indicates the index SNP, and a black bar indicates the top SNP.</p

Association results for variants showing the smallest <i>P</i>-values (top SNPs) in 31 regions surrounding previous GWAS-identified variants (index SNPs).

<p>Association results for variants showing the smallest <i>P</i>-values (top SNPs) in 31 regions surrounding previous GWAS-identified variants (index SNPs).</p

Results for selected top interactions among top marginal loci with p-value less than 5×10⁻⁵ in Phase I studies.

<p>P_het is the heterogeneity p-value.</p

Forest plot for meta-analysis results of GxG between rs1571218 and rs10879357.

<p>Box sizes are proportional to the inverse variance for each study and the lines depict the confidence intervals. The diamonds represent the fixed effects meta-analysis results, with the width of the diamond representing the confidence interval. The results of two advanced adenoma studies (HPFS Adv Adnm and NHS Adv Adnm) are shown at the bottom but not incorporated in the meta-analysis.</p

Regional interaction association plot for interacting region 5q21 with known CRC locus rs10795668.

<p>The left y-axis shows the -log10 of the meta-analysis interaction p value. The right y-axis shows the recombination rate. Each dot on the plot represents the result for one SNP. The diamond dot represents SNP rs367615 and the round dots represent other SNPs. Difference colors of SNPs indicate different LD strength between the corresponding SNP and rs367615, measured by r². The bottom of the figure shows the genes in the plotted region.</p

Studies in Genetics and Epidemiology Colorectal Cancer Consortium (GECCO).

a<p>Sample size excludes overlap with CCFR;</p>†<p>Sample sizes given only for subjects clustering with HapMap CEU population in PCA (for data that has undergone QC);</p>¶<p>Includes participants with data downloaded from dbGaP prostate and lung studies;*for adenoma, number and % colon does not include subjects with adenomas located in both colon and rectum.</p

An illustration of different two-SNP interaction models. SNP 1 has genotype AA, Aa and aa; SNP 2 has genotype BB, Bb, and bb. A and B are the major alleles for SNP1 and 2, respectively.

<p>Each entry in the tables represents the risk of the corresponding genotype combination relative to the baseline (AA/BB). (a) Multiplicative interaction model; (b) Unrestricted interaction model; (c) Average Risk Due to Interaction (ARDI) model.</p

Interaction pattern between rs10795668 and rs367615.

<p>Interaction pattern between rs10795668 and rs367615.</p