A prospective study of dietary and supplemental zinc intake and risk of type 2 diabetes depending on genetic variation in SLC30A8.
A prospective study of dietary and supplemental zinc intake and risk of type 2 diabetes depending on genetic variation in SLC30A8.
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DOI：
10.1186/s12263-017-0586-y
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发表时间：
2017
影响因子：
3.5
通讯作者：
Orho-Melander M
中科院分区：
文献类型：
--
作者：
Drake I;Hindy G;Ericson U;Orho-Melander M
溶质载体家族30成员8基因(SLC30A8)编码胰岛β细胞中的锌转运体，SLC30A8错义突变(rs13266634；C/T；R325W)的主要C等位基因与2型糖尿病(T2D)的风险增加有关。我们假设锌摄入量和T2D之间的关联可能被SLC30A8基因改变。我们在MalmöDiet和癌症研究队列中对没有心脏代谢性疾病病史的受试者进行了一项前瞻性研究(N=0.26132，38%男性；86%有基因数据)。锌的摄入量通过饮食问卷和食物记录进行评估。在中位数19年的随访中，发生了3676例T2D病例。以达到年龄为时间尺度的BMI-分层Cox比例风险回归模型被用来模拟总锌摄入量与膳食锌摄入量、锌补充剂用量、锌铁比以及T2D调整可能的混杂因素的风险之间的关系。锌总摄入量中位数为11.4 mg/d，膳食锌摄入量中位数为10.7 mg/d。补锌使用者(17%)的总锌摄入量中位数为22.4万毫克/天。膳食锌摄入量与T2D风险增加相关(P趋势：0.0001)。相比之下，我们观察到锌补充剂使用者患T2D的风险较低(HR=0.79，95%CI为0.70-0.89)。SLC30A8CC基因型与T2D的危险性相关(HR=1.16，95%CI为1.07~1.24)，且这种作用在BMI较高的人群中更强(P交互作用=0.007)。我们没有观察到SLC30A8基因对锌-T2D关联的显著影响。然而，SLC30A8型、体重指数和锌铁比之间存在三向交互作用(P交互作用=0.007)。在肥胖者中，高锌铁比对T2D风险具有保护性关联作用，而且这种作用在T等位基因携带者中明显更明显。补充锌和高锌铁摄入量比可能会降低T2D的风险，但这些关联可能会被肥胖和SLC30A8基因改变。这一发现暗示，当考虑补充锌预防T2D时，肥胖状况和SLC30A8基因可能都需要考虑在内。本文的在线版本(10.1186/s12263-0170586-y)包含向授权用户提供的补充材料。
The solute carrier family 30 member 8 gene (SLC30A8) encodes a zinc transporter in the pancreatic beta cells and the major C-allele of a missense variant (rs13266634; C/T; R325W) in SLC30A8 is associated with an increased risk of type 2 diabetes (T2D). We hypothesized that the association between zinc intake and T2D may be modified by the SLC30A8 genotype. We carried out a prospective study among subjects with no history cardio-metabolic diseases in the Malmö Diet and Cancer Study cohort (N = 26,132, 38% men; 86% with genotype data). Zinc intake was assessed using a diet questionnaire and food record. During a median follow-up of 19 years, 3676 T2D cases occurred. A BMI-stratified Cox proportional hazards regression model with attained age as the time scale was used to model the association between total and dietary zinc intake, zinc supplement use, zinc to iron ratio, and risk of T2D adjusting for putative confounding factors. The median total zinc intake was 11.4 mg/day, and the median dietary zinc intake was 10.7 mg/day. Zinc supplement users (17%) had a median total zinc intake of 22.4 mg/day. Dietary zinc intake was associated with increased risk of T2D (P trend < 0.0001). In contrast, we observed a lower risk of T2D among zinc supplement users (HR = 0.79, 95% CI 0.70–0.89). The SLC30A8 CC genotype was associated with a higher risk of T2D (HR = 1.16, 95% CI 1.07–1.24), and the effect was stronger among subjects with higher BMI (P interaction = 0.007). We observed no significant modification of the zinc-T2D associations by SLC30A8 genotype. However, a three-way interaction between SLC30A8 genotype, BMI, and zinc to iron ratio was observed (P interaction = 0.007). A high zinc to iron ratio conferred a protective associated effect on T2D risk among obese subjects, and the effect was significantly more pronounced among T-allele carriers. Zinc supplementation and a high zinc to iron intake ratio may lower the risk of T2D, but these associations could be modified by obesity and the SLC30A8 genotype. The findings implicate that when considering zinc supplementation for T2D prevention, both obesity status and SLC30A8 genotype may need to be accounted for. The online version of this article (10.1186/s12263-017-0586-y) contains supplementary material, which is available to authorized users.
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影响因子：
30.8
作者：
Flannick, Jason;Thorleifsson, Gudmar;Beer, Nicola L.;Jacobs, Suzanne B. R.;Grarup, Niels;Burtt, Noel P.;Mahajan, Anubha;Fuchsberger, Christian;Atzmon, Gil;Benediktsson, Rafn;Blangero, John;Bowden, Don W.;Brandslund, Ivan;Brosnan, Julia;Burslem, Frank;Chambers, John;Cho, Yoon Shin;Christensen, Cramer;Douglas, Desiree A.;Duggirala, Ravindranath;Dymek, Zachary;Farjoun, Yossi;Fennell, Timothy;Fontanillas, Pierre;Forsen, Tom;Gabriel, Stacey;Glaser, Benjamin;Gudbjartsson, Daniel F.;Hanis, Craig;Hansen, Torben;Hreidarsson, Astradur B.;Hveem, Kristian;Ingelsson, Erik;Isomaa, Bo;Johansson, Stefan;Jorgensen, Torben;Jorgensen, Marit Eika;Kathiresan, Sekar;Kong, Augustine;Kooner, Jaspal;Kravic, Jasmina;Laakso, Markku;Lee, Jong-Young;Lind, Lars;Lindgren, Cecilia M.;Linneberg, Allan;Masson, Gisli;Meitinger, Thomas;Mohlke, Karen L.;Molven, Anders;Morris, Andrew P.;Potluri, Shobha;Rauramaa, Rainer;Ribel-Madsen, Rasmus;Richard, Ann-Marie;Rolph, Tim;Salomaa, Veikko;Segre, Ayellet V.;Skaerstrand, Hanna;Steinthorsdottir, Valgerdur;Stringham, Heather M.;Sulem, Patrick;Tai, E. Shyong;Teo, Yik Ying;Teslovich, Tanya;Thorsteinsdottir, Unnur;Trimmer, Jeff K.;Tuomi, Tiinamaija;Tuomilehto, Jaakko;Vaziri-Sani, Fariba;Voight, Benjamin F.;Wilson, James G.;Boehnke, Michael;McCarthy, Mark I.;Njolstad, Pal R.;Pedersen, Oluf;Groop, Leif;Cox, David R.;Stefansson, Kari;Altshuler, David
通讯作者：
Altshuler, David
影响因子：
--
作者：
Cauchi S;Nead KT;Choquet H;Horber F;Potoczna N;Balkau B;Marre M;Charpentier G;Froguel P;Meyre D
通讯作者：
Meyre D
影响因子：
7.2
作者：
RICHARDSON, MT;LEON, AS;SERFASS, R
通讯作者：
SERFASS, R
影响因子：
11.1
作者：
Berglund, G;Nilsson, P;Lingärde, F
通讯作者：
Lingärde, F
影响因子：
4.2
作者：
Lönnerdal, B
通讯作者：
Lönnerdal, B