Total Zinc Intake May Modify the Glucose-Raising Effect of a Zinc Transporter (SLC30A8) Variant A 14-Cohort Meta-analysis

S Kanoni; JA Nettleton; MF Hivert; Z Ye; FJA van Rooij; D Shungin; E Sonestedt; JS Ngwa; MK Wojczynski; RN Lemaitre; S Gustafsson; JS Anderson; T Tanaka; G Hindy; G Saylor; F Renstrom; AJ Bennett; Cornelia Duijn; JC Florez; CS Fox; Bert Hofman; RC Hoogeveen; DK Houston; FB Hu; PF Jacques; I Johansson; L Lind; YM Liu; N McKeown; J Ordovas; JS Pankow; E.J.G. Sijbrands; AC Syvanen; André Uitterlinden; M Yannakoulia; M.C. Zillikens; NJ Wareham; I Prokopenko; S Bandinelli; NG Forouhi; LA Cupples; RJ Loos; G Hallmans; J Dupuis; C Langenberg; L Ferrucci; SB Kritchevsky; MI McCarthy; E Ingelsson; IB Borecki; JCM Witteman; M Orho-Melander; DS Siscovick; JB Meigs; PW Franks; GV Dedoussis

doi:10.2337/db11-0176

Total Zinc Intake May Modify the Glucose-Raising Effect of a Zinc Transporter (SLC30A8) Variant A 14-Cohort Meta-analysis

S Kanoni, JA Nettleton, MF Hivert, Z Ye, FJA van Rooij, D Shungin, E Sonestedt, JS Ngwa, MK Wojczynski, RN Lemaitre, S Gustafsson, JS Anderson, T Tanaka, G Hindy, G Saylor, F Renstrom, AJ Bennett, Cornelia Duijn, JC Florez, CS FoxBert Hofman, RC Hoogeveen, DK Houston, FB Hu, PF Jacques, I Johansson, L Lind, YM Liu, N McKeown, J Ordovas, JS Pankow, E.J.G. Sijbrands, AC Syvanen, André Uitterlinden, M Yannakoulia, M.C. Zillikens, NJ Wareham, I Prokopenko, S Bandinelli, NG Forouhi, LA Cupples, RJ Loos, G Hallmans, J Dupuis, C Langenberg, L Ferrucci, SB Kritchevsky, MI McCarthy, E Ingelsson, IB Borecki, JCM Witteman, M Orho-Melander, DS Siscovick, JB Meigs, PW Franks, GV Dedoussis

Research output: Contribution to journal › Article › Academic › peer-review

89 Citations (Scopus)

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 beta-cell function and glucose homeostasis. We tested the hypothesis that zinc intake could influence the glucose-raising effect of specific variants. RESEARCH DESIGN AND 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 (beta-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 (beta-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. Diabetes 60:2407-2416, 2011

Original language	Undefined/Unknown
Pages (from-to)	2407-2416
Number of pages	10
Journal	Diabetes
Volume	60
Issue number	9
DOIs	https://doi.org/10.2337/db11-0176
Publication status	Published - 2011

Research programs

EMC COEUR-09
EMC MM-01-25-01
EMC MM-01-39-09-A
EMC NIHES-01-64-01
EMC NIHES-01-64-02

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.2337/db11-0176

http://hdl.handle.net/1765/33302

Cite this

Kanoni, S., Nettleton, JA., Hivert, MF., Ye, Z., van Rooij, FJA., Shungin, D., Sonestedt, E., Ngwa, JS., Wojczynski, MK., Lemaitre, RN., Gustafsson, S., Anderson, JS., Tanaka, T., Hindy, G., Saylor, G., Renstrom, F., Bennett, AJ., Duijn, C., Florez, JC., ... Dedoussis, GV. (2011). Total Zinc Intake May Modify the Glucose-Raising Effect of a Zinc Transporter (SLC30A8) Variant A 14-Cohort Meta-analysis. Diabetes, 60(9), 2407-2416. https://doi.org/10.2337/db11-0176

@article{435a0522e32b4e0ca123eb23f8bdc546,

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 beta-cell function and glucose homeostasis. We tested the hypothesis that zinc intake could influence the glucose-raising effect of specific variants. RESEARCH DESIGN AND 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 (beta-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 (beta-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. Diabetes 60:2407-2416, 2011",

author = "S Kanoni and JA Nettleton and MF Hivert and Z Ye and {van Rooij}, FJA and D Shungin and E Sonestedt and JS Ngwa and MK Wojczynski and RN Lemaitre and S Gustafsson and JS Anderson and T Tanaka and G Hindy and G Saylor and F Renstrom and AJ Bennett and Cornelia Duijn and JC Florez and CS Fox and Bert Hofman and RC Hoogeveen and DK Houston and FB Hu and PF Jacques and I Johansson and L Lind and YM Liu and N McKeown and J Ordovas and JS Pankow and E.J.G. Sijbrands and AC Syvanen and Andr{\'e} Uitterlinden and M Yannakoulia and M.C. Zillikens and NJ Wareham and I Prokopenko and S Bandinelli and NG Forouhi and LA Cupples and RJ Loos and G Hallmans and J Dupuis and C Langenberg and L Ferrucci and SB Kritchevsky and MI McCarthy and E Ingelsson and IB Borecki and JCM Witteman and M Orho-Melander and DS Siscovick and JB Meigs and PW Franks and GV Dedoussis",

year = "2011",

doi = "10.2337/db11-0176",

language = "Undefined/Unknown",

volume = "60",

pages = "2407--2416",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association Inc.",

number = "9",

}

Kanoni, S, Nettleton, JA, Hivert, MF, Ye, Z, van Rooij, FJA, Shungin, D, Sonestedt, E, Ngwa, JS, Wojczynski, MK, Lemaitre, RN, Gustafsson, S, Anderson, JS, Tanaka, T, Hindy, G, Saylor, G, Renstrom, F, Bennett, AJ, Duijn, C, Florez, JC, Fox, CS, Hofman, B, Hoogeveen, RC, Houston, DK, Hu, FB, Jacques, PF, Johansson, I, Lind, L, Liu, YM, McKeown, N, Ordovas, J, Pankow, JS, Sijbrands, EJG, Syvanen, AC, Uitterlinden, A, Yannakoulia, M, Zillikens, MC, Wareham, NJ, Prokopenko, I, Bandinelli, S, Forouhi, NG, Cupples, LA, Loos, RJ, Hallmans, G, Dupuis, J, Langenberg, C, Ferrucci, L, Kritchevsky, SB, McCarthy, MI, Ingelsson, E, Borecki, IB, Witteman, JCM, Orho-Melander, M, Siscovick, DS, Meigs, JB, Franks, PW & Dedoussis, GV 2011, 'Total Zinc Intake May Modify the Glucose-Raising Effect of a Zinc Transporter (SLC30A8) Variant A 14-Cohort Meta-analysis', Diabetes, vol. 60, no. 9, pp. 2407-2416. https://doi.org/10.2337/db11-0176

TY - JOUR

T1 - Total Zinc Intake May Modify the Glucose-Raising Effect of a Zinc Transporter (SLC30A8) Variant A 14-Cohort Meta-analysis

AU - Kanoni, S

AU - Nettleton, JA

AU - Hivert, MF

AU - Ye, Z

AU - van Rooij, FJA

AU - Shungin, D

AU - Sonestedt, E

AU - Ngwa, JS

AU - Wojczynski, MK

AU - Lemaitre, RN

AU - Gustafsson, S

AU - Anderson, JS

AU - Tanaka, T

AU - Hindy, G

AU - Saylor, G

AU - Renstrom, F

AU - Bennett, AJ

AU - Duijn, Cornelia

AU - Florez, JC

AU - Fox, CS

AU - Hofman, Bert

AU - Hoogeveen, RC

AU - Houston, DK

AU - Hu, FB

AU - Jacques, PF

AU - Johansson, I

AU - Lind, L

AU - Liu, YM

AU - McKeown, N

AU - Ordovas, J

AU - Pankow, JS

AU - Sijbrands, E.J.G.

AU - Syvanen, AC

AU - Uitterlinden, André

AU - Yannakoulia, M

AU - Zillikens, M.C.

AU - Wareham, NJ

AU - Prokopenko, I

AU - Bandinelli, S

AU - Forouhi, NG

AU - Cupples, LA

AU - Loos, RJ

AU - Hallmans, G

AU - Dupuis, J

AU - Langenberg, C

AU - Ferrucci, L

AU - Kritchevsky, SB

AU - McCarthy, MI

AU - Ingelsson, E

AU - Borecki, IB

AU - Witteman, JCM

AU - Orho-Melander, M

AU - Siscovick, DS

AU - Meigs, JB

AU - Franks, PW

AU - Dedoussis, GV

PY - 2011

Y1 - 2011

N2 - 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 beta-cell function and glucose homeostasis. We tested the hypothesis that zinc intake could influence the glucose-raising effect of specific variants. RESEARCH DESIGN AND 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 (beta-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 (beta-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. Diabetes 60:2407-2416, 2011

AB - 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 beta-cell function and glucose homeostasis. We tested the hypothesis that zinc intake could influence the glucose-raising effect of specific variants. RESEARCH DESIGN AND 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 (beta-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 (beta-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. Diabetes 60:2407-2416, 2011

U2 - 10.2337/db11-0176

DO - 10.2337/db11-0176

M3 - Article

C2 - 21810599

SN - 0012-1797

VL - 60

SP - 2407

EP - 2416

JO - Diabetes

JF - Diabetes

IS - 9

ER -