Genetic Aspects of Latent Autoimmune Diabetes in Adults: A Mini-Review

Abstract

Diabetes is a multifactorial disease, caused by a complex interplay between environmental and genetic risk factors. Genetic determinants of particularly Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D) have been studied extensively, whereas well-powered studies of Latent Autoimmune Diabetes in Adults (LADA) are lacking. So far available studies support a clear genetic overlap between LADA and T1D, however, with smaller effect sizes of the T1D-risk variants in LADA as compared to T1D. A genetic overlap between LADA and T2D is less clear. However, recent studies, including large numbers of LADA patients, provide different lines of evidence to support a genetic overlap between T2D and LADA. The genetic predisposition to LADA is yet to be explored in a study design, like a genome- wide association study, which allows for analyses of the genetic predisposition independently of prior hypothesis about potential candidate genes. This type of study may facilitate the discovery of risk variants associated with LADA independently of T1D and T2D, and is central in order to determine if LADA should be considered as an independent diabetic subtype. Extended knowledge about the genetic predisposition to LADA may also facilitate stratification of the heterogeneous group of LADA patients, which may assist the choice of treatment. This mini-review summarizes current knowledge of the genetics of LADA, and discusses the perspectives for future studies.

Keywords: Genetics; HLA; LADA; PTPN22; TCF7L2; family history; latent autoimmune diabetes in adults..