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

Publication

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

Journal Paper/Review - Aug 1, 2011

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

Citation

Dedoussis G, Cupples L, Forouhi N, Bandinelli S, Prokopenko I, Wareham N, Zillikens M, Yannakoulia M, Uitterlinden A, Syvänen A, Sijbrands E, Pankow J, Loos R, Hallmans G, Franks P, Meigs J, Siscovick D, Orho-Melander M, Witteman J, Borecki I, Ingelsson E, McCarthy M, Kritchevsky S, Ferrucci L, Langenberg C, Dupuis J, Ordovas J, McKeown N, Liu Y, Tanaka T, Anderson J, Gustafsson S, Lemaitre R, Wojczynski M, Ngwa J, Sonestedt E, Shungin D, van Rooij F, Ye Z, Hivert M, Nettleton J, Hindy G, Saylor G, Lind L, Johansson I, Jacques P, Hu F, Houston D, Hoogeveen R, Hofman A, Fox C, Florez J, van Duijn C, Bennett A, Renström F, Kanoni S. Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: a 14-cohort meta-analysis. Diabetes 2011; 60:2407-16.

Type

Journal Paper/Review (English)

Journal

Diabetes 2011; 60

Publication Date

Aug 1, 2011

Issn Electronic

1939-327X

Pages

2407-16

Brief description/objective

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.