Association between anti-ZnT8 autoantibody specificities and SLC30A8 Arg325Trp variant in Japanese patients with type 1 diabetes
Association between anti-ZnT8 autoantibody specificities and SLC30A8 Arg325Trp variant in Japanese patients with type 1 diabetes
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DOI：
10.1007/s00125-008-1165-y
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发表时间：
2008-12-01
期刊：
影响因子：
8.2
通讯作者：
Eguchi, K.
中科院分区：
文献类型：
--
作者：
Kawasaki, E.;Uga, M.;Eguchi, K.
我们分析了对锌转运蛋白8（ZnT 8）的体液自身反应性与SLC 30 A8 rs 13266634多态性之间的关系，（Arg325Trp），用放射免疫法测定了270例1型糖尿病患者血清中抗ZnT 8的自身抗体（氨基酸268-369）和杂合构建体（CW-CR）。44个ZnT 8自身抗体阳性血清的基因组DNA被用来检查之间的关联反应ZnT 8结构和rs 13266634 genotype.75例患者反应的CW-CR杂交构建体，而37和36例患者反应的CW和CR结构，分别。所有CW或CR自身抗体阳性的血清均为CW-CR自身抗体阳性。在19例325 Arg（CC）基因型患者中，5%有CW特异性自身抗体，42%有CR特异性自身抗体，32%有双重反应性。相反，15例325 Trp（TT）基因型患者中有73%有CW特异性自身抗体，没有患者有CR特异性自身抗体，13%有双重反应性。10名CT基因型患者中有9名（90%）对CR或CW结构有反应。携带C等位基因的患者的CR抗体滴度显著高于TT纯合子（p
We analysed the association between humoral autoreactivity to zinc transporter-8 (ZnT8) and the SLC30A8 rs13266634 polymorphism (Arg325Trp), which is located at the most distal loop in the ZnT8 protein.Autoantibodies to ZnT8 were determined by RIA in 270 patients with type 1 diabetes using ZnT8 carboxy-terminal constructs (amino acids 268-369) carrying 325Trp(CW) and 325Arg(CR) and a hybrid construct (CW-CR). Forty-four ZnT8 autoantibody-positive sera with genomic DNA were used to examine the association between reactivity to ZnT8 constructs and the rs13266634 genotype.Seventy-five patients reacted to the CW-CR hybrid construct, whereas 37 and 36 patients reacted to the CW and CR constructs, respectively. All sera positive for either CW or CR autoantibodies were positive for CW-CR autoantibodies. Among 19 patients with a 325Arg(CC) genotype, 5% had CW-specific autoantibodies, 42% had CR-specific autoantibodies and 32% had dual reactivity. Conversely, 73% of 15 patients with the 325Trp(TT) genotype had CW-specific autoantibodies, no patients had CR-specific autoantibodies and 13% had dual reactivity. Nine of the ten patients (90%) with the CT genotype reacted with either CR or CW constructs. The titre of CR autoantibodies in patients carrying the C allele was significantly higher than that in TT homozygotes (p