Zinc transporter 8
Solute carrier family 30 (zinc transporter), member 8, also known as SLC30A8, is a human gene[1] that codes for a zinc transporter related to insulin secretion in humans. Certain alleles of this gene may increase the risk for developing type 2 diabetes, but a loss-of-function mutation appears to greatly reduce the risk of diabetes.[2]
Clinical significance
Association with type 2 diabetes (T2D)
12 rare variants in SLC30A8 have been identified through the sequencing or genotyping of approximately 150,000 individuals from 5 different ancestry groups. SLC30A8 contains a common variant (p.Trp325Arg), which is associated with T2D risk and levels of glucose and proinsulin.[3][4][5] Individuals carrying protein-truncating variants collectively had 65% reduced risk of T2D. Additionally, non-diabetic individuals from Iceland harboring a frameshift variant p.Lys34Serfs*50 demonstrated reduced glucose levels.[2] Earlier functional studies of SLC30A8 suggested that reduced zinc transport increased T2D risk.[6][7] Conversely, loss-of-function mutations in humans indicate that SLC30A8 haploinsufficiency protects against T2D. Therefore, ZnT8 inhibition can serve as a therapeutic strategy in preventing T2D.[2]
See also
References
- ^ "Entrez Gene: SLC30A8 solute carrier family 30 (zinc transporter), member 8".
- ^ a b c Flannick, Jason; et al. (2014). "Loss-of-function mutations in SLC30A8 protect against type 2 diabetes". Nature Genetics. doi:10.1038/ng.2915.
- ^ Dupis, J.; et al. (Feb 2010). "New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk". Nature Genetics. 42 (2): 105–16. doi:10.1038/ng.520. PMID 20081858.
- ^ Strawbridge, R.J.; et al. (October 2011). "Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes". Diabetes. 60 (10): 2624–34. doi:10.2337/db11-0415. PMC 3178302. PMID 21873549.
- ^ Morris, A.P.; et al. (Sep 2012). "Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes". Nature Genetics. 44 (9): 981–90. doi:10.1038/ng.2383. PMID 22885922.
- ^ Nicolson, T.J.; et al. (Sep 2009). "Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes–associated variants". Diabetes. 58 (9): 2070–83. doi:10.2337/db09-0551. PMID 19542200.
- ^ Rutter, G.A.; et al. "Think zinc: new roles for zinc in the control of insulin secretion". Islets. 2 (1): 49–50. doi:10.4161/isl.2.1.10259. PMID 21099294.
Further reading
External links
- Type 2 diabetes genes mapped out, BBC News article
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