By Amy Adams, MS

Reviewed By Jeremy Walston, MD
Last Updated September 15, 2000

If you or someone in your family has Type 2 diabetes, you may wonder if other family members are at risk. It turns out that Type 2 diabetes often runs in families and is also more common in some ethnic groups. In fact, researchers have found many genes that can effect your heritable risk for developing Type 2 diabetes.

Identifying Type 2 Diabetes Genes

Although researchers know from studying family histories that you can inherit a risk for Type 2 diabetes, they have had difficulty identifying specific gene mutations that cause the disease.

Some of the problems include:

• Number of genes: Many genes are involved in controlling our fuel intake and regulation. A mutation in any one gene will probably not lead to diabetes, but mutations in several genes could add up to pose an increased risk. Any two people with Type 2 diabetes may have mutations in a different subset of genes, making it hard for researchers to pinpoint high-risk mutations.
• Environmental influence: A person's lifestyle and environment play a large role in whether or not they develop Type 2 diabetes. Two people may have the same risk and the same gene mutations, but if one person controls their weight and exercises regularly, that person may not develop diabetes. If two people have the same mutation but different outcomes, researchers have a hard time distinguishing which genes are important in the disease.
• Inherited Lifestyle: We inherit more than just genes from our parents; we also inherit lifestyle. Poor eating habits and lack of exercise are learned behaviors that children can pick up from their parents. This type of inheritance has nothing to do with genes, and makes it hard for researchers to identify a genetic risk for diabetes.

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The Beta3-Adrenergic Receptor Gene

The Beta3-adrenergic receptor gene makes a protein in fat cells that is involved in determining how much fuel your body burns when you are resting. A mutation in this gene slows down how quickly a person burns fat — increasing their tendency to be obese. One specific mutation in this gene, called TRP64ARG, is almost four times more common in Pima Indians than in people of European descent, and is one and a half times more common in people of African or Mexican descent. The prevalence of the TRP64ARG gene mutation in these populations probably accounts at least in part for why these ethnic groups have a higher rate of Type 2 diabetes.

People with two copies of the TRP64ARG mutation: Are more obese Have slower metabolism Have a hard time losing weight Develop diabetes at an earlier age

People with two copies of the TRP64ARG mutation have a slower metabolism than people without the mutation. Therefore, they tend to be more obese — even in mutation carriers who do not go on to develop diabetes. They also have a harder time losing weight than the general population. In addition, people with the TRP64ARG mutation develop diabetes at an earlier age than Type 2 diabetics without the mutation. This mutation is not present in all Type 2 diabetics, but it appears to change the course of diabetes in those who carry it.

The TRP64ARG mutation causes the Beta3-adrenergic receptor gene to make a different protein sequence. The name is an abbreviation for the change in the protein caused by the mutation. The altered protein has the amino acid Arginine (ARG) at the 64th position, rather than the amino acid Tryptophan (TRP). This switch in amino acid building blocks prevents the protein from working properly.

The Beta3-adrenergic receptor gene is not the only gene that regulates how we metabolize fat. Researchers think that mutations in similar genes may also put a person at risk for diabetes. So far, they have not found common mutations in these genes that cause diabetes, but there is ongoing research in high-risk populations and families to find additional gene mutations.

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Genetic Testing

The genetics of Type 2 diabetes is complicated, with many different genes influencing a person's risk. Because of this array of genes, Type 2 diabetes is not inherited in a clearly dominant or recessive manner. Instead, a person may have one gene that increases their risk and other genes that decrease risk. Together, these genes, along with environmental factors, determine a person's overall risk for developing diabetes. With so many variables to consider, the medical community is a long way from a genetic test for Type 2 diabetes.

Although there is no genetic test for Type 2 diabetes, the American Diabetes Association recommends screening for diabetes onset every three years if you have diabetes in the family. Doctors screen for diabetes onset using a fasting glucose test or glucose tolerance test, which tells doctors if your blood glucose levels are unusually high.

References

Walston, J., et al. (1995). Time of onset of non-insulin dependent diabetes mellitus and genetic variation in the B(3)-adrenergic receptor gene. N Engl J Med, 333, 343-347.

Silver, K., et al. (1997). TRP64ARG beta 3-adrenergic receptor and obesity in Mexican Americans. Hum Genet, 101, 306-311.

Kadowaki, H., et al. (1995). A mutation in the beta 3-adrenergic receptor gene is associated with obesity and hyperinsulinemia in Japanese subjects. Biochem Biophys Res Commun, 215, 555-560.

Widen, E., et al. (1995). Association of a polymorphism in the B(3)-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns. N Engl J Med, 333, 348-351.

Clement, K., et al. (1995). Genetic variation in the B(3)-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. N Engl J Med, 333, 352-354.