Alvin Ho, Paula Jossan, Noah Zaitlen and Srinath Sanda*
Background: Type 1 diabetes patients lose residual β-cell function after diagnosis at variable rates affecting development of diabetes related complications. The cause of this variability is not understood. We hypothesized that common genetic variants in genes in the insulin secretion pathway would influence the natural history of type 1 diabetes. Methods: DNA samples and longitudinal insulin secretion data from 167 newly diagnosed type 1 diabetes patients were obtained. Participants were genotyped for common variants in insulin secretion pathway genes. Results: After accounting for age, high-risk HLA alleles, BMI Z-score, and gender in a mathematical model, a non-coding intronic variant (rs10513688) in the SLC2A2 gene correlated with rate of loss of insulin secretion over the first 12 months. To confirm the biological significance of this non-coding region we created a microdeletion in the homologous intronic region in mouse β-cells and observed reduced Slc2a2 and insulin expression suggesting a functional role for this non-coding region. Conclusion: This work suggests that a common genetic variant in SLC2A2 may associate with longitudinal decline in residual insulin secretion in patients with type 1 diabetes.
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