Total Zinc Intake May Modify the Glucose-Raising Effect of a Zinc Transporter (SLC30A8) Variant
نویسندگان
چکیده
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.
منابع مشابه
Total Zinc Intake May Modify the Glucose-Raising Effect of a Zinc Transporter (SLC30A8) Variant A 14-Cohort Meta-Analysis
of a Zinc Transporter (SLC30A8) Variant A 14-Cohort Meta-Analysis Stavroula Kanoni, Jennifer A. Nettleton, Marie-France Hivert, Zheng Ye, Frank J.A. van Rooij, Dmitry Shungin, Emily Sonestedt, Julius S. Ngwa, Mary K. Wojczynski, Rozenn N. Lemaitre, Stefan Gustafsson, Jennifer S. Anderson, Toshiko Tanaka, George Hindy, Georgia Saylor, Frida Renstrom, Amanda J. Bennett, Cornelia M. van Duijn, Jos...
متن کاملZinc-Associated Variant in SLC30A8 Gene Interacts With Gestational Weight Gain on Postpartum Glycemic Changes: A Longitudinal Study in Women With Prior Gestational Diabetes Mellitus
Zinc transporter 8 genetic variant SLC30A8 has been associated with postpartum risk of type 2 diabetes among women with gestational diabetes mellitus (GDM). Gestational weight gain is one of the strongest risk factors for postpartum hyperglycemia. We assessed the interaction between type 2 diabetes-associated SLC30A8 rs13266634 and gestational weight gain on 1-5 years of postpartum glycemic cha...
متن کاملThe Physiological Effects of Deleting the Mouse Slc30a8 Gene Encoding Zinc Transporter-8 Are Influenced by Gender and Genetic Background
OBJECTIVE The SLC30A8 gene encodes the islet-specific transporter ZnT-8, which is hypothesized to provide zinc for insulin-crystal formation. A polymorphic variant in SLC30A8 is associated with altered susceptibility to type 2 diabetes. Several groups have examined the effect of global Slc30a8 gene deletion but the results have been highly variable, perhaps due to the mixed 129SvEv/C57BL/6J gen...
متن کاملInteractions between zinc transporter-8 gene (SLC30A8) and plasma zinc concentrations for impaired glucose regulation and type 2 diabetes.
Although both SLC30A8 rs13266634 single nucleotide polymorphism and plasma zinc concentrations have been associated with impaired glucose regulation (IGR) and type 2 diabetes (T2D), their interactions for IGR and T2D remain unclear. Therefore, to assess zinc-SLC30A8 interactions, we performed a case-control study in 1,796 participants: 218 newly diagnosed IGR patients, 785 newly diagnosed T2D p...
متن کاملInsulin Storage and Glucose Homeostasis in Mice Null for the Granule Zinc Transporter ZnT8 and Studies of the Type 2 Diabetes–Associated Variants
OBJECTIVE Zinc ions are essential for the formation of hexameric insulin and hormone crystallization. A nonsynonymous single nucleotide polymorphism rs13266634 in the SLC30A8 gene, encoding the secretory granule zinc transporter ZnT8, is associated with type 2 diabetes. We describe the effects of deleting the ZnT8 gene in mice and explore the action of the at-risk allele. RESEARCH DESIGN AND ...
متن کامل