Genetics and Type 2 Diabetes - Part 2

A variant at the intron 3 in the genetic sequence of the CAPN10 gene has been shown to alter insulin production, the function of insulin, and the production of glucose by the liver. Specifically, the intron 3 of the CAPN10 gene can lead to a risk factor for diabetes because the normally present nucleotide called adenine is changed to the nucleotide called guanine. Therefore, a gene sequence of a G/G combination at this sequence is the abnormal gene sequence variant, and the normal sequence is the A/G combination. Two other regions, intron 6 and 13, in the CAPN10 gene, also increase the risk for diabetes. The G/G combination in the CAPN10 gene leads to insulin resistance.

The heaptocyte nuclear factor 4 alpha is located on chromosome 20. It is a gene that codes for a transcription factor, an enzyme that allows genes to be copied. Mutations in this gene lead to a decline in insulin secretion and can also lead to the loss of pancreatic beta cell function. Mutations in the HNF4A can be passed on from one generation to another. Therefore, diabetes which results from a mutation in the HNF4A gene can be passed on from mother or father to a child, giving the child a predisposition for developing diabetes. The Ashkenazi Jewish population are at an increased risk for having a mutation in this gene.

If you want to know your risk for developing diabetes, or if you want to know if you may have a genetic predisposition for developing diabetes, you can consult a genetic counselor. A genetic counselor can take your family history and draw a medical family tree to see if anyone in your family has had diabetes or the potential reasons why the other family member may have developed diabetes.

After the family history tree is collected, the genetic counselor can come up with risk calculations which will show your specific risks from your family history and background. After that information is given, the genetic counselor can talk with you about what genetic tests you might have done. After you have a genetic test done, the results are provided, and more specific risk factors can be given for your risk of developing diabetes based on a combination of your family history and genetic information.

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Barroso J, Luan J, Middelberg RP, et al. Candidate gene association study in type 2 diabetes indicates a role for genes involved in beta-Cell function as well as insulin action. PLoS Biol 2003; 1:E20-E20.

Thomas H, Jaschkowitz K, Bulman M, et al. A distant upstream promoter of the HNF-4alpha gene connects the transcription factors involved in maturity-onset diabetes of the young. Hum Mol Genet 2001; 10:2089-2097.

Love-Gregory LD, Wasson J, Ma J, et al. A common polymorphism in the upstream promoter region of the hepatocyte nuclear factor-4 alpha gene on chromosome 20q is associated with type 2 diabetes and appears to contribute to the evidence for linkage in an Ashkenazi jewish population. Diabetes 2004; 53:1134-1140.