PMC:3543924 / 9023-11944 JSONTXT

{"project":"2_test","denotations":[{"id":"23346036-22885924-44840049","span":{"begin":839,"end":841},"obj":"22885924"},{"id":"23346036-20879971-44840050","span":{"begin":1578,"end":1580},"obj":"20879971"},{"id":"23346036-19020323-44840051","span":{"begin":2260,"end":2262},"obj":"19020323"},{"id":"23346036-19020324-44840052","span":{"begin":2264,"end":2266},"obj":"19020324"}],"text":"Perspectives in Genetic Studies of GDM\nGWA studies have opened a new era in diabetes research. Our knowledge on the genetic predisposition of GDM as well as T2DM is expected to increase even faster as next-generation sequencing technology is applied to this field. There should be even larger GWA studies on GDM, and GWA meta-analyses should be available. In this way, we could find variants that have smaller effect sizes but are more specific to GDM than T2DM. In order to understand the genetic determinants of glucose and insulin concentration during pregnancy, genetic associations regarding these quantitative traits should be investigated. A fast way is to see whether genetic variants that are known to affect glucose or insulin concentration in the normal population also affect glucose or insulin concentration during pregnancy [29]. In addition, a GWA study on glucose or insulin concentration during pregnancy should also be helpful. In this way, we would be able to better understand the pathophysiology of GDM.\nBy definition, GDM encompasses women with pre-exiting T2DM, maturity onset diabetes of the young (MODY), or even type 1 diabetes patients that were not diagnosed previously. It would be important to know the proportion of MODY patients that constitute GDM. In particular, about 15% of GDM patients remain diabetic at early postpartum periods, and a significant portion of these subjects might fall into the category of MODY. The contribution of genetic variants known to cause MODY, such as GCK and HNF1A, in GDM has been reviewed in recent literature [30]. However, whole-exome sequencing will provide us with better bird's eye view on the contribution of MODY genes in GDM. In addition, it might be able to find novel MODY genes in those who have persistent diabetes after GDM pregnancy and also have a strong family history of diabetes.\nOne of the first steps in translating the genetic information into clinical practice would be to predict the future development of T2DM in GDM women. GDM women are at particularly high risk of developing T2DM and require preventive measures and early screening of T2DM. Genetic information might improve our prediction of T2DM in women with a history of GDM. This is an area of active research [31, 32], and we are looking forward to studies that use genotype risk scores in predicting T2DM in GDM women. A similar approach could also be applied in predicting GDM, as more genetic variants associated with GDM are expected to be revealed.\nThe functional consequences of the current common genetic variants identified through GWA studies of GDM are not well understood yet. It is not known whether they are markers in linkage disequilibrium with nearby causal variants or whether they have unknown but relevant functional roles. Next-generation sequencing might give answers to these questions, but a huge number of samples and much effort will be required."}