Zinc transporter 8 autoantibodies and their association with SLC30A8 and HLA-DQ genes differ between immigrant and Swedish patients with newly diagnosed type 1 diabetes in the Better Diabetes Diagnosis study.
Zinc transporter 8 autoantibodies and their association with SLC30A8 and HLA-DQ genes differ between immigrant and Swedish patients with newly diagnosed type 1 diabetes in the Better Diabetes Diagnosis study.
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DOI：
10.2337/db11-1659
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发表时间：
2012-10
期刊：
影响因子：
7.7
通讯作者：
Better Diabetes Diagnosis Study Group
中科院分区：
文献类型：
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作者：
Delli AJ;Vaziri-Sani F;Lindblad B;Elding-Larsson H;Carlsson A;Forsander G;Ivarsson SA;Ludvigsson J;Kockum I;Marcus C;Samuelsson U;Örtqvist E;Groop L;Bondinas GP;Papadopoulos GK;Lernmark Å;Better Diabetes Diagnosis Study Group
我们研究了是否锌转运蛋白8自身抗体（ZnT 8A，精氨酸ZnT 8-RA，色氨酸ZnT 8-WA，谷氨酰胺ZnT 8-QA变体）不同移民和瑞典患者之间由于不同的SLC 30 A8，HLA-DQ，或两者的多态性。新诊断的自身免疫性（≥1种胰岛自身抗体）1型糖尿病患者（n = 2，964，<18岁，55%为男性）在糖尿病更佳诊断研究中得到确认。确定了两个亚组：瑞典人（n = 2，160，73%）和移民（非瑞典人; n = 212，7%）。非瑞典人的ZnT 8-WA频率（38%）低于瑞典人（50%），这与非瑞典人（37%）的SLC 30 A8 CT+TT（RW+WW）基因型频率低于瑞典人（54%）一致。ZnT 8-RA（分别为57%和58%）没有差异，尽管CC（RR）基因型在非瑞典人（63%）比瑞典人（46%）更高的频率。我们测试了这种不一致是否是由于HLA-DQ为2/X（2/2; 2/y; y是任何东西，但2或8），这是一个主要的基因型在非瑞典人（40%）相比，瑞典人（14%）。仅在非瑞典人中，2/X（2/2; 2/y）与ZnT 8-WA和ZnT 8-QA呈负相关，但与ZnT 8-RA无关。分子模拟显示相关ZnT 8-R肽与DQ 2不结合，部分解释了可能缺乏对ZnT 8-R的耐受性。在非瑞典人的诊断中，ZnT 8-RA而不是ZnT 8-WA的存在可能是由于HLA-DQ 2和SLC 30 A8 CC（RR）基因型的影响。
We examined whether zinc transporter 8 autoantibodies (ZnT8A; arginine ZnT8-RA, tryptophan ZnT8-WA, and glutamine ZnT8-QA variants) differed between immigrant and Swedish patients due to different polymorphisms of SLC30A8, HLA-DQ, or both. Newly diagnosed autoimmune (≥1 islet autoantibody) type 1 diabetic patients (n = 2,964, <18 years, 55% male) were ascertained in the Better Diabetes Diagnosis study. Two subgroups were identified: Swedes (n = 2,160, 73%) and immigrants (non-Swedes; n = 212, 7%). Non-Swedes had less frequent ZnT8-WA (38%) than Swedes (50%), consistent with a lower frequency in the non-Swedes (37%) of SLC30A8 CT+TT (RW+WW) genotypes than in the Swedes (54%). ZnT8-RA (57 and 58%, respectively) did not differ despite a higher frequency of CC (RR) genotypes in non-Swedes (63%) than Swedes (46%). We tested whether this inconsistency was due to HLA-DQ as 2/X (2/2; 2/y; y is anything but 2 or 8), which was a major genotype in non-Swedes (40%) compared with Swedes (14%). In the non-Swedes only, 2/X (2/2; 2/y) was negatively associated with ZnT8-WA and ZnT8-QA but not ZnT8-RA. Molecular simulation showed nonbinding of the relevant ZnT8-R peptide to DQ2, explaining in part a possible lack of tolerance to ZnT8-R. At diagnosis in non-Swedes, the presence of ZnT8-RA rather than ZnT8-WA was likely due to effects of HLA-DQ2 and the SLC30A8 CC (RR) genotypes.
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影响因子：
16.2
作者：
通讯作者：
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影响因子：
2.7
作者：
Egefjord L;Jensen JL;Bang-Berthelsen CH;Petersen AB;Smidt K;Schmitz O;Karlsen AE;Pociot F;Chimienti F;Rungby J;Magnusson NE
通讯作者：
Magnusson NE
影响因子：
5.4
作者：
Kiviniemi, Minna;Hermann, Robert;Ilonen, Jorma
通讯作者：
Ilonen, Jorma
影响因子：
4.2
作者：
Keltner, Zachary;Meyer, Jennifer A.;Reid, Gavin E.
通讯作者：
Reid, Gavin E.
影响因子：
8.2
作者：
Boesgaard, T. W.;Zilinskaite, J.;Hansen, T.
通讯作者：
Hansen, T.