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

Kanoni, Stavroula; Nettleton, Jennifer A.; Hivert, Marie-France; Ye, Zheng; van Rooij, Frank J. A.; Shungin, Dmitry LU ; Sonestedt, Emily LU ; Ngwa, Julius S.; Wojczynski, Mary K. and Lemaitre, Rozenn N., et al. (2011) In Diabetes 60(9). p.2407-2416
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.... (More)
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 (Less)
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Contribution to journal
publication status
published
subject
in
Diabetes
volume
60
issue
9
pages
2407 - 2416
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000294699600024
  • scopus:80052880822
ISSN
1939-327X
DOI
10.2337/db11-0176
language
English
LU publication?
yes
id
af4335e8-1c25-42f8-8466-95b6b77ecd47 (old id 2187044)
date added to LUP
2011-11-01 07:53:17
date last changed
2017-11-12 03:48:25
@article{af4335e8-1c25-42f8-8466-95b6b77ecd47,
  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       = {Kanoni, Stavroula and Nettleton, Jennifer A. and Hivert, Marie-France and Ye, Zheng and van Rooij, Frank J. A. and Shungin, Dmitry and Sonestedt, Emily and Ngwa, Julius S. and Wojczynski, Mary K. and Lemaitre, Rozenn N. and Gustafsson, Stefan and Anderson, Jennifer S. and Tanaka, Toshiko and Hindy, George and Saylor, Georgia and Renstrom, Frida and Bennett, Amanda J. and van Duijn, Cornelia M. and Florez, Jose C. and Fox, Caroline S. and Hofman, Albert and Hoogeveen, Ron C. and Houston, Denise K. and Hu, Frank B. and Jacques, Paul F. and Johansson, Ingegerd and Lind, Lars and Liu, Yongmei and McKeown, Nicola and Ordovas, Jose and Pankow, James S. and Sijbrands, Eric J. G. and Syvanen, Ann-Christine and Uitterlinden, Andre G. and Yannakoulia, Mary and Zillikens, M. Carola and Wareham, Nick J. and Prokopenko, Inga and Bandinelli, Stefania and Forouhi, Nita G. and Cupples, L. Adrienne and Loos, Ruth J. and Hallmans, Goran and Dupuis, Josee and Langenberg, Claudia and Ferrucci, Luigi and Kritchevsky, Stephen B. and McCarthy, Mark I. and Ingelsson, Erik and Borecki, Ingrid B. and Witteman, Jacqueline C. M. and Orho-Melander, Marju and Siscovick, David S. and Meigs, James B. and Franks, Paul and Dedoussis, George V.},
  issn         = {1939-327X},
  language     = {eng},
  number       = {9},
  pages        = {2407--2416},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Total Zinc Intake May Modify the Glucose-Raising Effect of a Zinc Transporter (SLC30A8) Variant A 14-Cohort Meta-analysis},
  url          = {http://dx.doi.org/10.2337/db11-0176},
  volume       = {60},
  year         = {2011},
}