title: Exploring the Association Between Demographics, SLC30A8 Genotype, and Human Islet Content of Zinc, Cadmium, Copper, Iron, Manganese and Nickel.
abstract: A widely prevalent single nucleotide polymorphism, rs13266634 in the SLC30A8 gene encoding the zinc transporter ZnT8, is associated with an increased risk for T2DM. ZnT8 is mostly expressed in pancreatic insulin-producing islets of Langerhans. The effect of this variant on the divalent metal profile in human islets is unknown. Additionally, essential and non-essential divalent metal content of human islets under normal environmental exposure conditions has not been described. We therefore examined the correlation of zinc and other divalent metals in human islets with rs13266634 genotype and demographic characteristics. We found that the diabetes risk genotype C/C at rs13266634 is associated with higher islet Zn concentration (C/C genotype: 16792 ± 1607, n = 22, C/T genotype: 11221 ± 1245, n = 18 T/T genotype: 11543 ± 6054, n = 3, all values expressed as mean nmol/g protein ± standard error of the mean, p = 0.040 by ANOVA). A positive correlation between islet cadmium content and both age (p = 0.048, R2= 0.09) and female gender (women: 36.88 ± 4.11 vs men: 21.22 ± 3.65 nmol/g protein, p = 0.007) was observed. Our results suggest that the T2DM risk allele C is associated with higher islet zinc levels and support prior evidence of cadmium's higher bioavailability in women and its long tissue half-life.
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
authors.forename: Winifred P
authors.initials: WP
authors.lastname: Wong
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
authors.forename: Norrina B
authors.initials: NB
authors.lastname: Allen
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Meyers
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
authors.forename: Emma O
authors.initials: EO
authors.lastname: Link
authors.affiliation: Division of Transplant Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Chemistry of Life Processes Institute and Department of Chemistry, Northwestern University, Evanston, IL, 60208, USA.
authors.forename: Keith W
authors.initials: KW
authors.lastname: MacRenaris
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA. m-muayed@northwestern.edu.
authors.forename: Malek
authors.initials: M
authors.lastname: El Muayed
mesh_terms: D000328:Adult; D000367:Age Factors; D000483:Alleles; D002104:Cadmium / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007501:Iron / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008345:Manganese / Q000378:metabolism; D008670:Metals / Q000378:metabolism*; D008875:Middle Aged; D009532:Nickel / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D015032:Zinc / Q000378:metabolism*; D000075703:Zinc Transporter 8 / Q000235:genetics* / Q000378:metabolism
chemical_list: D008670:Metals; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; D002104:Cadmium; D008345:Manganese; D003300:Copper; D009532:Nickel; D007501:Iron; D015032:Zinc