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Association between anti-ZnT8 autoantibody specificities and SLC30A8 Arg325Trp variant in Japanese patients with type 1 diabetes.

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Title: Association between anti-ZnT8 autoantibody specificities and SLC30A8 Arg325Trp variant in Japanese patients with type 1 diabetes.
Authors: Kawasaki, Eiji / Uga, Mho / Nakamura, Kazuhiko T. / Kuriya, Genpei / Satoh, T / Fujishima, Keiichiro / Ozaki, M / Abiru, Norio / Yamasaki, H / Wenzlau, Janet M. / Davidson, Howard W. / Hutton, J C / Eguchi, K
Issue Date: Dec-2008
Publisher: Springer Berlin
Citation: Diabetologia, 51(12), pp.2299-2302; 2009
Abstract: AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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 < 0.0001). In contrast, the titre of CW autoantibodies in patients carrying a T allele was significantly higher than that in CC homozygotes (p < 0.005). No evidence of an association between rs13266634 and type 1 diabetes was observed. CONCLUSIONS/INTERPRETATION: These results indicate that variant residue at amino acid 325 is a key determinant of humoral autoreactivity to ZnT8 and that the SLC30A8 genotype is an important determinant of autoantibody specificity.
Keywords: Autoantibodies / Epitope / Genetics / Japanese population / SLC30A8 / Type 1 diabetes / Zinc transporter-8
URI: http://hdl.handle.net/10069/22262
ISSN: 0012186X
DOI: 10.1007/s00125-008-1165-y
PubMed ID: 18850084
Rights: © Springer-Verlag 2008 / The original publication is available at www.springerlink.com
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/22262

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