Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: a 14-cohort meta-analysis.
Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: a 14-cohort meta-analysis.
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DOI：
10.2337/db11-0176
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发表时间：
2011-09
期刊：
影响因子：
7.7
通讯作者：
Dedoussis GV
中科院分区：
文献类型：
--
作者：
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;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
在全基因组关联研究中，许多基因变异与葡萄糖稳态和2型糖尿病有关。锌是一种必需的微量营养素，对β细胞功能和葡萄糖稳态非常重要。我们测试了锌摄入量可能影响特定变种的升糖效应的假设。我们进行了14个队列的荟萃分析，以评估已知的20个与血糖性状和锌代谢相关的遗传变异与饮食锌摄入量(食物来源)的交互作用，以及5个队列的荟萃分析，以评估与总锌摄入量(食物来源和补充剂)的交互作用对无糖尿病的欧洲血统个体空腹血糖水平的影响。我们观察到总锌摄入量与较低的空腹血糖水平显著相关(β系数±SE：每1 mg/天锌摄入量：−0.0012±0.0003 mmoL/L，汇总P值=0.0003)，而膳食锌摄入量的相关性不显著。我们发现总锌摄入量与空腹血糖水平的SLC30A8rs11558471变异之间存在名义上显著的交互作用(β系数±每个A等位基因SE对于总锌摄入量增加1 mg/天：−0.0017±0.0006 mmoL/L，总交互作用P值=0.005)；这一结果表明，与不携带血糖升高A等位基因的个体相比，携带该等位基因的个体的总锌摄入量与空腹血糖之间存在更强的负相关。其他的交互作用测试都没有统计学意义。我们的结果表明，较高的总锌摄入量可能会减弱rs11558471 SLC30A8(锌转运体)变异体的升糖效应。我们的发现也支持了更高的总锌摄入量与更低的空腹血糖水平之间的关联的证据。
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. 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. 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. 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.