Total Zinc Intake May Modify the Glucose-Raising Effect of a Zinc Transporter (SLC30A8) Variant

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Total Zinc Intake May Modify the Glucose-Raising Effect of a Zinc Transporter (SLC30A8) Variant

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Title: Total Zinc Intake May Modify the Glucose-Raising Effect of a Zinc Transporter (SLC30A8) Variant
Author: Kanoni, Stavroula; Nettleton, Jennifer A.; Hivert, Marie-France; Ye, Zheng; van Rooij, Frank J.A.; Shungin, Dmitry; Sonestedt, Emily; Ngwa, Julius S.; Wojczynski, Mary K.; Lemaitre, Rozenn N.; Gustafsson, Stefan; Tanaka, Toshiko; Hindy, George; Saylor, Georgia; Renstrom, Frida; Bennett, Amanda J.; van Duijn, Cornelia M.; Hoogeveen, Ron C.; Houston, Denise K.; Jacques, Paul F.; Johansson, Ingegerd; Lind, Lars; Liu, Yongmei; McKeown, Nicola; Ordovas, Jose; Pankow, James S.; Sijbrands, Eric J.G.; Syvänen, Ann-Christine; Uitterlinden, André G.; Yannakoulia, Mary; Zillikens, M. Carola; Wareham, Nick J.; Prokopenko, Inga; Bandinelli, Stefania; Forouhi, Nita G.; Cupples, L. Adrienne; Loos, Ruth J.; Hallmans, Goran; Dupuis, Josée; Langenberg, Claudia; Ferrucci, Luigi; Kritchevsky, Stephen B.; McCarthy, Mark I.; Ingelsson, Erik; Borecki, Ingrid B.; Witteman, Jacqueline C.M.; Orho-Melander, Marju; Siscovick, David S.; Franks, Paul W.; Dedoussis, George V.; Anderson, Jennifer S.; Florez, Jose Carlos; Fox, Caroline; Hofman, Albert; Hu, Frank B.; Meigs, James Benjamin

Note: Order does not necessarily reflect citation order of authors.

Citation: Kanoni, Stavroula, Jennifer A. Nettleton, Marie-France Hivert, Zheng Ye, Frank J.A. van Rooij, Dmitry Shungin, Emily Sonestedt, et al. 2011. Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant. Diabetes 60(9): 2407-2416.
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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 β-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.
Published Version: doi:10.2337/db11-0176
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