Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: A 14-cohort meta-analysis

Stavroula Kanoni; Jennifer A. Nettleton; Marie France Hivert; Zheng Ye; Frank J A Van Rooij; Dmitry Shungin; Emily Sonestedt; Julius S. Ngwa; Mary K. Wojczynski; Rozenn N. Lemaitre; Stefan Gustafsson; Jennifer S. Anderson; Toshiko Tanaka; George Hindy; Georgia Saylor; Frida Renstrom; Amanda J. Bennett; Cornelia M. Van Duijn; Jose C. Florez; Caroline S. Fox; Albert Hofman; Ron C. Hoogeveen; Denise K. Houston; Frank B. Hu; Paul F. Jacques; Ingegerd Johansson; Lars Lind; Yongmei Liu; Nicola McKeown; Jose Ordovas; James S. Pankow; Eric J G Sijbrands; Ann Christine Syvänen; André G. Uitterlinden; Mary Yannakoulia; M. Carola Zillikens; Nick J. Wareham; Inga Prokopenko; Stefania Bandinelli; Nita G. Forouhi; L. Adrienne Cupples; Ruth J. Loos; Goran Hallmans; Josée Dupuis; Claudia Langenberg; Luigi Ferrucci; Stephen B. Kritchevsky; Mark I. McCarthy; Erik Ingelsson; Ingrid B. Borecki; Jacqueline C M Witteman; Marju Orho-Melander; David S. Siscovick; James B. Meigs; Paul W. Franks; George V. 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

Stavroula Kanoni, Jennifer A. Nettleton, Marie France Hivert, Zheng Ye, Frank J A Van Rooij, Dmitry Shungin, Emily Sonestedt, Julius S. Ngwa, Mary K. Wojczynski, Rozenn N. Lemaitre, Stefan Gustafsson, Jennifer S. Anderson, Toshiko Tanaka, George Hindy, Georgia Saylor, Frida Renstrom, Amanda J. Bennett, Cornelia M. Van Duijn, Jose C. Florez, Caroline S. FoxAlbert Hofman, Ron C. Hoogeveen, Denise K. Houston, Frank B. Hu, Paul F. Jacques, Ingegerd Johansson, Lars Lind, Yongmei Liu, Nicola McKeown, Jose Ordovas, James S. Pankow, Eric J G Sijbrands, Ann Christine Syvänen, André G. Uitterlinden, Mary Yannakoulia, M. Carola Zillikens, Nick J. Wareham, Inga Prokopenko, Stefania Bandinelli, Nita G. Forouhi, L. Adrienne Cupples, Ruth J. Loos, Goran Hallmans, Josée Dupuis, Claudia Langenberg, Luigi Ferrucci, Stephen B. Kritchevsky, Mark I. McCarthy, Erik Ingelsson, Ingrid B. Borecki, Jacqueline C M Witteman, Marju Orho-Melander, David S. Siscovick, James B. Meigs, Paul W. Franks, George V. Dedoussis

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

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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 b-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 (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.

Original language	English (US)
Pages (from-to)	2407-2416
Number of pages	10
Journal	Diabetes
Volume	60
Issue number	9
DOIs	https://doi.org/10.2337/db11-0176
State	Published - Sep 2011
Externally published	Yes

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

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10.2337/db11-0176

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Kanoni, S., Nettleton, J. A., Hivert, M. F., Ye, Z., Van Rooij, F. J. A., Shungin, D., Sonestedt, E., Ngwa, J. S., Wojczynski, M. K., Lemaitre, R. N., Gustafsson, S., Anderson, J. S., Tanaka, T., Hindy, G., Saylor, G., Renstrom, F., Bennett, A. J., Van Duijn, C. M., Florez, J. C., ... Dedoussis, G. V. (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

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, Van Duijn, CM, Florez, JC, Fox, CS, Hofman, A, Hoogeveen, RC, Houston, DK, Hu, FB, Jacques, PF, Johansson, I, Lind, L, Liu, Y, McKeown, N, Ordovas, J, Pankow, JS, Sijbrands, EJG, Syvänen, AC, Uitterlinden, AG, 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

@article{75e5a7f6cfcd4e0d97760d84af78d797,

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 b-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 (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.",

author = "Stavroula Kanoni and Nettleton, {Jennifer A.} and Hivert, {Marie France} and Zheng Ye and {Van Rooij}, {Frank J A} and Dmitry Shungin and Emily Sonestedt and Ngwa, {Julius S.} and Wojczynski, {Mary K.} and Lemaitre, {Rozenn N.} and Stefan Gustafsson and Anderson, {Jennifer S.} and Toshiko Tanaka and George Hindy and Georgia Saylor and Frida Renstrom and Bennett, {Amanda J.} and {Van Duijn}, {Cornelia M.} and Florez, {Jose C.} and Fox, {Caroline S.} and Albert Hofman and Hoogeveen, {Ron C.} and Houston, {Denise K.} and Hu, {Frank B.} and Jacques, {Paul F.} and Ingegerd Johansson and Lars Lind and Yongmei Liu and Nicola McKeown and Jose Ordovas and Pankow, {James S.} and Sijbrands, {Eric J G} and Syv{\"a}nen, {Ann Christine} and Uitterlinden, {Andr{\'e} G.} and Mary Yannakoulia and Zillikens, {M. Carola} and Wareham, {Nick J.} and Inga Prokopenko and Stefania Bandinelli and Forouhi, {Nita G.} and Cupples, {L. Adrienne} and Loos, {Ruth J.} and Goran Hallmans and Jos{\'e}e Dupuis and Claudia Langenberg and Luigi Ferrucci and Kritchevsky, {Stephen B.} and McCarthy, {Mark I.} and Erik Ingelsson and Borecki, {Ingrid B.} and Witteman, {Jacqueline C M} and Marju Orho-Melander and Siscovick, {David S.} and Meigs, {James B.} and Franks, {Paul W.} and Dedoussis, {George V.}",

year = "2011",

month = sep,

doi = "10.2337/db11-0176",

language = "English (US)",

volume = "60",

pages = "2407--2416",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association Inc.",

number = "9",

}

TY - JOUR

T1 - Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant

T2 - A 14-cohort meta-analysis

AU - Kanoni, Stavroula

AU - Nettleton, Jennifer A.

AU - Hivert, Marie France

AU - Ye, Zheng

AU - Van Rooij, Frank J A

AU - Shungin, Dmitry

AU - Sonestedt, Emily

AU - Ngwa, Julius S.

AU - Wojczynski, Mary K.

AU - Lemaitre, Rozenn N.

AU - Gustafsson, Stefan

AU - Anderson, Jennifer S.

AU - Tanaka, Toshiko

AU - Hindy, George

AU - Saylor, Georgia

AU - Renstrom, Frida

AU - Bennett, Amanda J.

AU - Van Duijn, Cornelia M.

AU - Florez, Jose C.

AU - Fox, Caroline S.

AU - Hofman, Albert

AU - Hoogeveen, Ron C.

AU - Houston, Denise K.

AU - Hu, Frank B.

AU - Jacques, Paul F.

AU - Johansson, Ingegerd

AU - Lind, Lars

AU - Liu, Yongmei

AU - McKeown, Nicola

AU - Ordovas, Jose

AU - Pankow, James S.

AU - Sijbrands, Eric J G

AU - Syvänen, Ann Christine

AU - Uitterlinden, André G.

AU - Yannakoulia, Mary

AU - Zillikens, M. Carola

AU - Wareham, Nick J.

AU - Prokopenko, Inga

AU - Bandinelli, Stefania

AU - Forouhi, Nita G.

AU - Cupples, L. Adrienne

AU - Loos, Ruth J.

AU - Hallmans, Goran

AU - Dupuis, Josée

AU - Langenberg, Claudia

AU - Ferrucci, Luigi

AU - Kritchevsky, Stephen B.

AU - McCarthy, Mark I.

AU - Ingelsson, Erik

AU - Borecki, Ingrid B.

AU - Witteman, Jacqueline C M

AU - Orho-Melander, Marju

AU - Siscovick, David S.

AU - Meigs, James B.

AU - Franks, Paul W.

AU - Dedoussis, George V.

PY - 2011/9

Y1 - 2011/9

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 b-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 (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.

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 b-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 (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.

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JO - Diabetes

JF - Diabetes

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ER -

Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: A 14-cohort meta-analysis

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