- slide 1 of 6
Diabetes is a medical condition that results from the body not being able to produce insulin, a hormone which helps convert sugars into glucose molecules and transports the sugars into cells to provide energy for our daily lives. When glucose builds up in the blood, instead of going into cells as it normally should, the buildup of glucose can damage our organs, such as the heart, kidney, eyes and nerves, and also potentially lead to changes in some metabolic brain functions.
There is a clear link for genetics being a risk factor in developing diabetes. When a gene mutation occurs, the protein that is made after a gene (or set of genes) is expressed, can change the function of a protein. If some parts of a protein are missing, or just changed in shape, the protein may not function as it normally would. This can lead to the development of a disease.
Knowing how a gene mutation can lead to different shapes of a protein can help scientists develop medications that can target specific change patterns. Moreover, even if a person has a genetic mutation that has been associated with the development of a disease, that does not necessarily mean the person will develop the disease. Certain factors need to be in place for the disease to develop. Some examples include environmental exposure to toxins, or a poor diet.
In the case of diabetes, a person can have a gene mutation in the genes that have been linked to diabetes, but if the person keeps his blood sugar and glucose at a healthy level, he can lower his chance of diabetes developing, because the damage that could have been done to the organs may no longer occur.
- slide 2 of 6
Calpain 10 enzyme (CAPN10)
The Calpain 10 enzyme (CAPN10), which is produced from the CAPN10 gene, works by breaking down proteins. Certain regions of this gene (which is located at the long arm of chromosome 2) that do not code for any genetic material, have been associated with a threefold increase for the risk of Type 2 diabetes in Mexican Americans.
- slide 3 of 6
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.
- slide 4 of 6
Hepatocyte Nuclear Factor 4 Alpha (HNF4A)
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.
- slide 5 of 6
ConclusionIf 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 performed, 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.
- slide 6 of 6
ReferencesHanis CL, et al. A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2. Nat Genet 1996; 13:161-166. 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.