oa Understanding Susceptibility Gene Loci Of Gestational Diabetes Mellitus

One of the fundamental goals of genetic research is to understand the pattern of heritability associated with the manifestation of various complex diseases. Elucidation of underlying genetic variation associated with common traits is one of the major challenges faced by clinical researchers. Gestational diabetes Mellitus (GDM) is multifactorial disorder of pregnancy. GDM refers to abnormal glucose tolerance that is first identified or diagnosed during pregnancy. GDM has long term impacts on the health of mother, developing fetus and child. Women and their offspring with history of GDM are at a greater risk of developing Type 2 Diabetes Mellitus (T2DM). GDM increases the risk of adverse pregnancy outcomes, including preeclampsia, birth injuries, macrosomia and neonatal hypoglycemia, respiratory distress syndrome, neonatal cardiac dysfunction and stillbirth. It is estimated that 4% of pregnancies in the United States are complicated with GDM; however, rates of GDM are significantly increasing with an overall increased prevalence of diabetes. It is reported that prevalence of GDM varies considerably among racial and ethnic groups. Genetic causes of this disease are uncovered by many recent studies. A systematic review of genetic association studies of GDM was performed by using Pubmed navigator. Key terms used were GDM, genetics, genetic variants, genome wide association studies, genetic risk factors and genetic susceptibility and loci. Functional studies of GLUT1, FOXC2, IRS1, PPARGC1 and UCP2 genes have data suggesting an influence of these genes on GDM. Genetic variants that are common in GDM and T2DM are documented in several promising studies. Genetic variants of CAPN10, MBL2, KCNJ11, ABCC8, ND1, TCF7L2, ADIPOQ and PAI1 genes are associated with the development of both GDM and T2D. However, six genes are widely studied and all of them reported to have significant association with the risk of GDM are TCF7L2, GCL, KCNJ11, CDKAL1, IGF2BP2 and MTNR1B. It is therefore, determined that some susceptibility loci are unique to GDM and can be used in future as markers for identifying women with a high risk of GDM. There is an increasing need of replication of these studies in other populations. Identification of genetic variants in specific populations will significantly contribute to our understanding of the pathogenesis of GDM and will ultimately improve our prediction of GDM and future of T2DM.