Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: a 14-cohort meta-analysis.
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.
Kanoni, S; Nettleton, JA; Hivert, M-F; 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, A-C; Uitterlinden, AG; Yannakoulia, M; Zillikens, MC; MAGIC Investigators, ; 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
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