title: Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: a 14-cohort meta-analysis.
abstract: OBJECTIVE
  Many genetic variants have been associated with glucose homeostasis and type 2 diabetes in genome-wide association studies. Zinc is an essential micronutrient that is important for β-cell function and glucose homeostasis. We tested the hypothesis that zinc intake could influence the glucose-raising effect of specific variants.
  
  
  METHODS
  We conducted a 14-cohort meta-analysis to assess the interaction of 20 genetic variants known to be related to glycemic traits and zinc metabolism with dietary zinc intake (food sources) and a 5-cohort meta-analysis to assess the interaction with total zinc intake (food sources and supplements) on fasting glucose levels among individuals of European ancestry without diabetes.
  
  
  RESULTS
  We observed a significant association of total zinc intake with lower fasting glucose levels (β-coefficient ± SE per 1 mg/day of zinc intake: -0.0012 ± 0.0003 mmol/L, summary P value = 0.0003), while the association of dietary zinc intake was not significant. We identified a nominally significant interaction between total zinc intake and the SLC30A8 rs11558471 variant on fasting glucose levels (β-coefficient ± SE per A allele for 1 mg/day of greater total zinc intake: -0.0017 ± 0.0006 mmol/L, summary interaction P value = 0.005); this result suggests a stronger inverse association between total zinc intake and fasting glucose in individuals carrying the glucose-raising A allele compared with individuals who do not carry it. None of the other interaction tests were statistically significant.
  
  
  CONCLUSIONS
  Our results suggest that higher total zinc intake may attenuate the glucose-raising effect of the rs11558471 SLC30A8 (zinc transporter) variant. Our findings also support evidence for the association of higher total zinc intake with lower fasting glucose levels.
authors.affiliation: Department of Nutrition-Dietetics, Harokopio University, Athens, Greece. stavroula.kanoni@sanger.ac.uk
authors.forename: Stavroula
authors.initials: S
authors.lastname: Kanoni
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Nettleton
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Hivert
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ye
authors.forename: Frank J A
authors.initials: FJ
authors.lastname: van Rooij
authors.forename: Dmitry
authors.initials: D
authors.lastname: Shungin
authors.forename: Emily
authors.initials: E
authors.lastname: Sonestedt
authors.forename: Julius S
authors.initials: JS
authors.lastname: Ngwa
authors.forename: Mary K
authors.initials: MK
authors.lastname: Wojczynski
authors.forename: Rozenn N
authors.initials: RN
authors.lastname: Lemaitre
authors.forename: Stefan
authors.initials: S
authors.lastname: Gustafsson
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Anderson
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.forename: George
authors.initials: G
authors.lastname: Hindy
authors.forename: Georgia
authors.initials: G
authors.lastname: Saylor
authors.forename: Frida
authors.initials: F
authors.lastname: Renstrom
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Bennett
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Jose C
authors.initials: JC
authors.lastname: Florez
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Ron C
authors.initials: RC
authors.lastname: Hoogeveen
authors.forename: Denise K
authors.initials: DK
authors.lastname: Houston
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: Paul F
authors.initials: PF
authors.lastname: Jacques
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Johansson
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.forename: Nicola
authors.initials: N
authors.lastname: McKeown
authors.forename: Jose
authors.initials: J
authors.lastname: Ordovas
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
authors.forename: Eric J G
authors.initials: EJ
authors.lastname: Sijbrands
authors.forename: Ann-Christine
authors.initials: AC
authors.lastname: Syvänen
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Mary
authors.initials: M
authors.lastname: Yannakoulia
authors.forename: M Carola
authors.initials: MC
authors.lastname: Zillikens
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Inga
authors.initials: I
authors.lastname: Prokopenko
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: Nita G
authors.initials: NG
authors.lastname: Forouhi
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: Loos
authors.forename: Goran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Josée
authors.initials: J
authors.lastname: Dupuis
authors.forename: Claudia
authors.initials: C
authors.lastname: Langenberg
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Kritchevsky
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.forename: Jacqueline C M
authors.initials: JC
authors.lastname: Witteman
authors.forename: Marju
authors.initials: M
authors.lastname: Orho-Melander
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.forename: James B
authors.initials: JB
authors.lastname: Meigs
authors.forename: Paul W
authors.initials: PW
authors.lastname: Franks
authors.forename: George V
authors.initials: GV
authors.lastname: Dedoussis
mesh_terms: D001786:Blood Glucose / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D015032:Zinc / Q000008:administration & dosage* / Q000378:metabolism*; D000075703:Zinc Transporter 8
chemical_list: D001786:Blood Glucose; D027682:Cation Transport Proteins; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; D015032:Zinc