Genetic Insights Through Genome Wide Association Studies in Type 2 Diabetes Mellitus will Lead to New Therapeutics
Pp. 210-240 (31)
Marcel G. M. Wolfs, Naishi Li, Jingyuan Fu, Cisca Wijmenga, Timon W. van Haeften and Marten H. Hofker
Type 2 diabetes is a disorder of dysregulated glucose homeostasis. Normal
glucose homeostasis is a complex process involving several interacting mechanisms,
such as insulin secretion, insulin sensitivity, glucose production, and glucose uptake. The
dysregulation of one or more of these mechanisms due to environmental and/or genetic
factors, can lead to a defective glucose homeostasis. Hyperglycemia is managed by
augmenting insulin secretion and/or interaction with hepatic glucose production, as well
as by decreasing dietary caloric intake and raising glucose metabolism through exercise.
Although these interventions can delay disease progression and correct blood glucose
levels, they are not able to cure the disease or stop its progression entirely. Better
management of type 2 diabetes is sorely needed. Advances in genotyping techniques and
the availability of large patient cohorts have made it possible to identify common genetic
variants associated with type 2 diabetes through genome-wide association studies
(GWAS). So far, genetic variants on 50 loci have been identified. Most of these loci
contain or lie close to genes that were not previously linked to diabetes and they may thus
harbor targets for new drugs. It is also hoped that further genetic studies will pave the way
for predictive genetic screening. The newly discovered candidate genes for type 2
diabetes can be classified based on their presumed molecular function, and we discuss the
relation between these gene classes and current treatments. We go on to consider whether
the new genes provide opportunities for developing alternative drug therapies.
Type 2 diabetes, drug targets, genetics, personalized medicine.
Department of Pathology and Medical Biology, Medical Biology Section, Molecular Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.