Short Report

SLC30A8 (ZnT8) Polymorphism is Associated with Young Age at Type 1 Diabetes Onset

Henning Gohlke¹, Uta Ferrari², Kerstin Koczwara², Ezio Bonifacio², Thomas Illig¹, Anette-G. Ziegler²

Manuscript submitted April 27, 2008; resubmitted May 13, 2008; accepted May 14, 2008.

Keywords: type 1 diabetes, zinc transporter, ZnT-8, SLC30A8, genotype, beta-cell dysfunction, age of onset

Abstract

It was recently shown that the major allele of the SLC30A8 (zinc transporter 8, ZnT8) single nucleotide polymorphism (SNP) rs13266634 was associated with type 2 diabetes and with reduced insulin secretion in non-diabetic relatives. Because of its role in beta-cell function, we hypothesized that this candidate SNP may confer increased susceptibility for beta-cell destruction in type 1 diabetes. We analyzed SLC30A8 genotypes in 874 patients with type 1 diabetes and 1021 control subjects. No difference in allele and genotype frequencies of the SLC30A8 SNP rs13266634 was found between patients and controls. Analysis with respect to age at type 1 diabetes onset, however, showed that patients with a diabetes onset before age 5 years had an increased prevalence of the cytosine (C) allele (risk allele, 82%) and the homozygous CC genotype (65%) compared to patients who developed type 1 diabetes after age 5 years (67% and 49%; p < 0.01) and compared to controls (69% and 48%; p < 0.03). These data suggest that genetic susceptibility for beta-cell dysfunction in the presence of autoimmunity may lead to accelerated progression and early manifestation of the disease.

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