A specific genetic variant, rs13266634 (c.973C>T; p.ARG325TRP) in zinc transporter SLC30A8/ZnT8, is associated with protection against Type-2 Diabetes, suggesting it may be actionable for predicting and preventing POHG.
A common ZnT8 gene (<i>SLC30A8</i>) polymorphism increases the risk of type 2 diabetes mellitus (T2DM), and rare mutations may present protective effects.
However, those with later onset type 1 diabetes had a modestly lower type 1 diabetes genetic risk score (0.268 vs 0.279; p < 0.001 [expected type 2 diabetes population median, 0.231]), a higher islet autoantibody prevalence (GAD-, islet antigen 2 [IA2]- or zinc transporter protein 8 [ZnT8]-positive) of 78% at 13 years vs 62% at 26 years of diabetes duration; (p = 0.02), and were less likely to identify as having type 1 diabetes (79% vs 100%; p < 0.001) vs those with young-onset disease.
We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 × 10<sup>-3</sup>) and candidate genes from knockout mice (P = 5.2 × 10<sup>-3</sup>).
Our study revealed an unexpected role of ZnT8 in regulating peripheral 5-HT biogenesis and intestinal microenvironment, which might contribute to the increased risk of obesity and type 2 diabetes.
Association between "solute carrier family 30 member 8" (SLC30A8) gene polymorphism and susceptibility to type 2 diabetes mellitus in Chinese Han and minority populations: an updated meta-analysis.
Our group and others showed that altered ZnT8 function may be involved in the pathogenesis of type 2 diabetes, indicating that the precise control of zinc homeostasis is crucial for maintaining health and preventing various diseases, including lifestyle-associated diseases.
Thus, variants in the SLC30A8 gene, encoding the vesicular/granular zinc transporter ZnT8, are associated with altered insulin release and increased T2D risk while the zinc importer ZIP12 is implicated in pulmonary hypertension.
The second set of genes LIM homeobox transcription factor 1 alpha (LMX1A), solute carrier family 30 member 8 (SLC30A8) is associated with insulin metabolism and resistance, a feature of some patients in whom type 2 diabetes is an accompanying comorbidity of vestibular neuritis.
A total of 556 healthy controls and 413 T2DM patients were genotyped for ZnT8Arg325Trp polymorphism confirming the association of Arg-325 variant with an increased T2DM risk (OR = 1.35 95% C.I: 1.10-1.66; p = 0.0044).
Therefore, individuals of Chinese descent with the C allele of <i>SLC30A8</i> gene 807C/T polymorphism may be more susceptible to developing T2DM, while individuals with the T allele may be protected against T2DM.