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Diabetic Genetics: A Complex Picture

Article

Have any specific genes been identified for type 1 or type 2 diabetes? If so, howmany genes are involved?

Have any specific genes been identified for type 1 or type 2 diabetes? If so, howmany genes are involved?
-MD

The answer to your question depends on the level of proof one requiresto establish that a particular gene is a "diabetes gene." Associationstudies show that certain genetic polymorphisms are more commonin persons who have diabetes than in those who do not.1,2 Linkagestudies demonstrate that a particular genetic locus is shared by relatedpersons with diabetes more often than would be expected based on chance.In some instances, researchers have determined the location of a gene buthave not been able to identify the gene.

Other trials have found associations or links between certain genes andtraits associated with diabetes, such as obesity or kidney disease, or with unusualforms of diabetes, such as those characterized by mitochondrial mutations;however, these genes are not necessarily linked to type 1 or type 2diabetes.

Type 1 diabetes. Linkage studies have strongly implicated 2 genetic regionsin type 1 diabetes: HLA and INS. It is unclear how the genes in theseregions influence the development of diabetes; they are neither necessary norsufficient to cause type 1 diabetes. Many other genes have also been implicatedin type 1 diabetes. However, these genes either exert less influence or theirinfluence is not as uniform across families as that of HLA and INS.

Type 2 diabetes. Dozens of genes have been implicated in type 2 diabetes.One of these, CAPN10, may exert a modest influence in many persons with diabetes,but it is neither necessary nor sufficient to cause the disease. Many formsof maturity-onset diabetes of youth (an unusual, highly inheritable form ofdiabetes) seem to be caused by a single gene.

In most persons, many genes probably contribute in small ways to an overallgenetic burden that allows diabetes to develop in a particular environment.It also seems likely that differences exist in the combinations of genes that putpersons at risk for type 2 diabetes. The genetics of diabetes is extremely complex.We are just beginning to glimpse some of the genes involved, and we canonly start to guess at the big picture.

-John B. Buse, MD, PhD, CDE
   Associate Professor of Medicine
   University of North Carolina at Chapel Hill School of Medicine

References:

REFERENCES:1. Froguel P, Velho G. Genetic determinants of type 2 diabetes. Recent Prog Horm Res. 2001;56:91-105.
2. Redondo MJ, Fain PR, Eisenbarth GS. Genetics of type 1A diabetes. Recent Prog Horm Res. 2001;56:69-89.

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