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Nutrient-Gene Interactions

Investigation of Lymphocyte Gene Expression for Use as Biomarkers for Zinc Status in Humans¹

Karl B. Andree^*, Jihye Kim, Catherine P. Kirschke^*, Jeff P. Gregg^**, HeeYoung Paik, Hyojee Joung, Leslie Woodhouse^*, Janet C. King and Liping Huang^*,,2

^* Western Human Nutrition Research Center, Agriculture Research Service, U.S. Department of Agriculture; Department of Food and Nutrition, Seoul National University, Seoul, South Korea; ^** Department of Medical Pathology, University of California Davis Medical Center; The School of Public Health, Seoul National University, Seoul, South Korea; Division of Nutritional Genomics, Children’s Hospital Oakland Research Institute, Oakland, CA; and Department of Nutrition and Rowe Program in Genetics, University of California at Davis, Davis, CA 95616

²To whom correspondence should be addressed. E-mail: lhuang{at}whnrc.usda.gov.

A bioassay for zinc status in humans has been sought due to the importance of zinc, an essential trace metal, for many divergent functions in the human body; however, a sensitive bioassay for zinc status in humans is lacking. To address this issue, we established gene expression profiles of human lymphoblastoid cells treated with 0 or 30 µmol/L ZnSO₄ using microarray technology. A limited number of genes were responsive to 30 µmol/L zinc based on the analysis of Affymetrix human genome U133A GeneChips. We also examined the gene expression patterns of zinc transporters in human lymphoblastoid cells using quantitative RT-PCR analysis. ZNT1 was upregulated in lymphoblastoid cells, whereas ZIP1 was downregulated in response to the increased zinc concentrations in the culture media. To evaluate the potential applications of using both zinc transporter genes as biomarkers of zinc status, we measured the expression levels of ZIP1 and ZNT1 in the peripheral leukocytes collected from 2 different age groups of Korean women. After administration of a zinc supplement (22 mg zinc gluconate/d for 27 d), ZIP1 expression decreased by 17% (P < 0.01) and 21% (P < 0.05) in the peripheral leukocytes collected from 15 young (20–25 y) and 10 elderly (64–75 y) subjects, respectively. ZNT1 expression was not affected by taking the zinc supplement. These data suggest a potential application of ZIP1 as a biomarker of zinc status in humans.

KEY WORDS: • zinc transporter • zinc supplementation • quantitative RT-PCR • microarray • humans

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