Zinc transporter 8

Twelve 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.{{cite journal|last1=Dupis|first1=J.|title=New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.|journal=Nature Genetics|doi=10.1038/ng.520|pmid=20081858|volume=42|issue=2|date=Feb 2010|pages=105–16|display-authors=etal|pmc=3018764}}{{cite journal|last1=Strawbridge|first1=R.J.|title=Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.|journal=Diabetes|doi=10.2337/db11-0415|pmid=21873549|url=http://diabetes.diabetesjournals.org/content/60/10/2624|volume=60|issue=10|pmc=3178302|date=October 2011|pages=2624–34|display-authors=etal}}{{cite journal|last1=Morris|first1=A.P.|title=Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes.|journal=Nature Genetics|doi=10.1038/ng.2383|pmid=22885922|volume=44|issue=9|date=Sep 2012|pages=981–90|display-authors=etal|pmc=3442244}} 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. Earlier functional studies of SLC30A8 suggested that reduced zinc transport increased T2D risk.{{cite journal|last1=Nicolson|first1=T.J.|title=Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes–associated variants.|journal=Diabetes|doi=10.2337/db09-0551|pmid=19542200|url=http://diabetes.diabetesjournals.org/content/58/9/2070|volume=58|issue=9|date=Sep 2009|pages=2070–83|display-authors=etal|pmc=2731533}}{{cite journal|last1=Rutter|first1=G.A.|title=Think zinc: new roles for zinc in the control of insulin secretion.|journal=Islets|doi=10.4161/isl.2.1.10259|pmid=21099294|volume=2|issue=1|pages=49–50|display-authors=etal|year=2010|doi-access=free}} 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.

• Solute carrier family

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• [http://news.bbc.co.uk/2/hi/health/6342855.stm Type 2 diabetes genes mapped out], BBC News article

Category:Solute carrier family

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