Biology:SLC30A8
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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". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=169026.
- ↑ 2.0 2.1 2.2 Flannick, Jason (2014). "Loss-of-function mutations in SLC30A8 protect against type 2 diabetes". Nature Genetics 46: 357–363. doi:10.1038/ng.2915. PMID 24584071.
- ↑ Dupis, J. (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. PMC 3018764. http://www.nature.com/ng/journal/v42/n2/full/ng.520.html.
- ↑ Strawbridge, R.J. (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. PMID 21873549. PMC 3178302. http://diabetes.diabetesjournals.org/content/60/10/2624.
- ↑ Morris, A.P. (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. PMC 3442244. http://www.nature.com/ng/journal/v44/n9/full/ng.2383.html.
- ↑ Nicolson, T.J. (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. PMC 2731533. http://diabetes.diabetesjournals.org/content/58/9/2070.
- ↑ Rutter, G.A.. "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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