Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: a 14-cohort meta-analysis.
Kanoni S., Nettleton JA., Hivert MF., Ye Z., van Rooij FJ., 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 EJ., Syvänen AC., Uitterlinden AG., Yannakoulia M., Zillikens MC., MAGIC Investigators None., 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 JC., Orho-Melander M., Siscovick DS., Meigs JB., Franks PW., Dedoussis GV.
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.