Type 2 Diabetes Genetics: Beyond GWAS

Abstract

The global epidemic of type 2 diabetes mellitus (T2D) is one of the most challenging problems of the 21st century leading cause of and the fifth death worldwide. Substantial evidence suggests that T2D is a multifactorial disease with a strong genetic component. Recent genome-wide association studies (GWAS) have successfully identified and replicated nearly 75 susceptibility loci associated with T2D and related metabolic traits, mostly in Europeans, and some in African, and South Asian populations. The GWAS serve as a starting point for future genetic and functional studies since the mechanisms of action by which these associated loci influence disease is still unclear and it is difficult to predict potential implication of these findings in clinical settings. Despite extensive replication, no study has unequivocally demonstrated their clinical role in the disease management beyond progression to T2D from impaired glucose tolerance. However, these studies are revealing new molecular pathways underlying diabetes etiology, gene-environment interactions, epigenetic modifications, and gene function. This review highlights evolving progress made in the rapidly moving field of T2D genetics that is starting to unravel the pathophysiology of a complex phenotype and has potential to show clinical relevance in the near future.

Association of the FABP2 Ala54Thr polymorphism with type 2 diabetes, obesity, and metabolic syndrome: a population-based case-control study and a systematic meta-analysis

“…According to the latest statistics from the International Diabetes Federation (IDF), the number of diabetes patients will rise from 366 million in 2011 to 552 million by 2030 (Sanghera and Blackett, 2012). The prevalence of obesity has increased at an alarming rate worldwide over past decades.…”

Особливий Випадок Інсулінорезистентності В Дівчинки 12 Років (Синдром Рабсона — Менденхолла)

“…Результати першого повно-геномного дослідження були опубліковані у 2007 році, вони повідомляли про дев'ять генів, пов'язаних із роз-витком цукрового діабету типу 2, у подальшому їх чис-ло поступово збільшувалося (табл. 1) [3][4][5].…”

Tip 2 diyabetin moleküler genetik temeli; Son gelişmeler

“…Yapılan genetik risk skorlama çalışmalarında oluşturulan genetik modellerin AUC değeri ~0.60 şeklin-de oldukça zayıf olarak tespit edilmektedir (120). Çünkü tanımlanmış mevcut varyantlar tip 2 diyabet kalıtımının yalnızca %10-15'ini açıklayabilmektedir (115,126). Ayrıca henüz tanımlanmamış başka genetik varyantların mevcut bulunması ve hiperglisemi ile tanımlanan ve oldukça heterojen durumlar ortaya koyan T2DM'nin belki de henüz tanımlanmayan birçok alt tipi bulunması bu duruma neden olmaktadır.…”