Zinc–rs13266634 and the Arrival of Diabetes Pharmacogenetics: The “Zinc Mystique”
- 1Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
- 2Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD
- 3Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
- 4Division of Endocrinology, Nutrition, and Metabolism, University of Maryland School of Medicine, Baltimore, MD
- Corresponding author: Nisa M. Maruthur, .
Advances in our understanding of the genetics of type 2 diabetes have been astronomical over the past decade with more than 100 single nucleotide polymorphisms (SNPs) associated with modest increases in diabetes risk and differences in related traits such as fasting glucose (1,2). However, these SNPs have contributed more to elucidating biologic pathways than predicting diabetes risk (3). Nonetheless, the most promising work suggests that we are on the cusp of being able to use genetic information to individualize treatment for type 2 diabetes prevention and management (4,5). The promise of pharmacogenetics is predicated on the existence of known individual variation in response to interventions and the strong biologic basis for genetic variation as a primary, immutable difference between individuals.
rs13266634 is one of the most consistently replicated diabetes risk variants (odds ratio of 1.14 for the R allele) (6). This SNP encodes a C→T base substitution in the SLC30A8 gene, resulting in a change in the coded protein (Arg325Trp or R325W). The frequency of the diabetes risk R allele is 91.5%, 71.7%, and 56.7% in Africans, Europeans, and Asians, respectively (1,000 Genomes).
The SLC30A8 gene encodes zinc transporter-8 (ZnT8). This transporter is specific to pancreatic islets and is …