Type II Diabetes – Genetic Connections

Genes involved in Type 2 diabetes
Genes involved in Type 2 diabetes

According to the American Diabetes Association, 9.3% of the US population has diabetes (2012 numbers).  Diabetes was the 7th leading cause of death in the US in 2010.  The genes involved in increasing risk for type-2 diabetes  indicate some of the variations in causes: insulin release, metabolic syndrome, response to sugar, and zinc deficiency.   Knowing how you are genetically susceptible to diabetes may help you to modify your diet appropriately.

Genes involved in type-2 diabetes:

SLC30A8

A zinc transporter gene, SLC30A8, has been identified as being associated with type 2 diabetes in a number of different studies.  Insulin contains a high amount of zinc, and zinc is also involved in other functions in the pancreas.   Zinc is believed to play an important role in insulin production and secretion.  Higher plasma concentrations of zinc are associated with lower risk of diabetes – especially for those without the SLC30A8 polymorphism [ref].    There are several studies on the influence of zinc supplementation with regards to diabetes and the SLC30A8 polymorphism.  [1, 2, 3]  The SLC30A8 polymorphism is associated with reduce insulin secretion, but not with insulin resistance. [ref]

There are quite a few new research studies on this gene.  One study from 2014 states that (emphasis added):

As expected, a strong interaction was observed for the SLC30A8 rs13266634 variant and plasma zinc concentrations in relation to T2D and IGR&T2D. The inverse association between increasing plasma zinc concentrations and T2D could significantly attenuate in the CT and CC genotype groups compared with in the TT genotype group. We also observed that the association between the CC genotype and T2D was mitigated by increasing plasma zinc concentrations.

Check your 23andMe results for rs13266634:

  • TT: normal risk for type 2 diabetes
  • CT: somewhat higher than normal risk for type 2 diabetes
  • CC:  1.5 – 3x higher risk of type 2 diabetes [ref]

For zinc, the U.S. recommended daily allowance is 11 mg/day for men and 8 mg/day for women.  Zinc supplementation can interact with other minerals.  The University of Oregon has a good resource for more information on types of zinc and interactions: Linus Pauling Institute Zinc.

HHEX

HHEX (homeobox) is another gene with polymorphisms that are associated with higher risk of developing type 2 diabetes.  The HHEX protein interacts with signaling molecules and plays a role in embryonic development of the liver, thyroid, and pancreas.  A European study in 2007 found that rs7923837 was associated with impaired glucose-stimulated insulin response. [ref]  A meta analysis from 2010 showed that:

…the risk allele of rs1111875 and rs7923837 within the HHEX gene were associated with reduced β-cell secretion capacity, which was measured as the first and second phase of insulin response in the OGTT. Detailed mechanisms of the influence of HHEX variants on the insulin secretion remain a matter of speculation. However, Tanaka et al. (45) demonstrated that HHEX may regulate β-cell development and/or function through the activation of hepatocyte nuclear factor 1α. [ref]

Check your 23andMe results for rs7923837:

  • GG: 3.2x risk for type 2 diabetes
  • AG: 1.9x risk for type 2 diabetes
  • AA:  normal risk of type 2 diabetes
Check your 23andMe results for rs1111875:

  • GG: increased risk for type 2 diabetes (OR = 1.36) [ref]
  • AG: increased risk for type 2 diabetes (OR =1.16)
  • AA:  normal risk of type 2 diabetes

TCF7L2

A strong genetic risk factor for type 2 diabetes is a polymorphism in the TCF7L2 gene.  It is thought that the TCF7L2 gene is involved in controlling blood sugar levels. It plays a role in adipogenesis (formation of fat cells), and it has been associated with glucose intolerce and impaired insulin secretion. [ref]

The CT/TT genotypes of SNP rs7903146 strongly predicted future T2D in 2 independent cohorts (Swedish and Finnish). The risk T allele was associated with impaired insulin secretion, incretin effects, and enhanced rate of hepatic glucose production. TCF7L2 expression in human islets was increased 5-fold in T2D, particularly in carriers of the TT genotype. Overexpression of TCF7L2 in human islets reduced glucose-stimulated insulin secretion. In conclusion, the increased risk of T2D conferred by variants in TCF7L2 involves the enteroinsular axis, enhanced expression of the gene in islets, and impaired insulin secretion. [ref]

Check your 23andMe results for rs7903146:

  • TT: 2x increased risk of type 2 diabetes
  • CT: 1.4x increased risk of type 2 diabetes
  • CC:  normal risk of type 2 diabetes

KCNJ11

One more gene associated with type-2 diabetes is the KCNJ11 gene.  The KCNJ11 gene codes a protein involved in insulin release.  Sugar (glucose) activates this protein which releases insulin from the pancreas.  The T allele gives a decreased insulin response to glucose. It is also associated with plasma leptin levels. [ref] [ref]

Check your 23andMe results for rs5219:

  • TT: 2.5x increased risk of type 2 diabetes (snpedia)
  • CT: 1.3x increased risk of type 2 diabetes
  • CC:  normal risk of type 2 diabetes

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