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Diabetes mellitus types: Key genetic determinants and risk assessment

Author(s): Dhilleswara Rao Vana, Dattatreya Adapa, Prasad VSS, Amarendranath Choudhury and Garima Ahuja

The characteristic symptom of diabetes is consistently elevated levels of blood sugar. This is instigated either by complete lack of insulin production (type 1 diabetes), reduced level of insulin production (type 2 diabetes) or insulin resistance (inability of body cells to take up glucose). Other types of diabetes include maturity onset of diabetes of the young (MODY), a form of type 2 diabetes and gestational diabetes which affects pregnant women mostly in second or third trimester. The term type-3-diabetes is now being used for insulin resistance in brain. Apart from environmental and dietary causes which pose the risk of diabetes, genetic constitution and gene mutations execute the manifestation of diabetes. So far, several hundreds of genes having genomic, metabolic and immunological functions have been associated with different forms of diabetes. Due to complexity in diabetes etiology, involvement of multiple genetic factors and overlap between phenotypes, the treatment for diabetes remains a major challenge. Single gene mutations can be potentially targeted therapeutically; however, the prevalence of single gene mutations in diabetic condition is rare. Comprehensive analysis of genes and genetic variants relevant to diabetes enables development of effective treatment or interventional strategies. The current literature survey was conducted and reviewed to identify studies that proposed the genetic basis for specific subtypes of diabetes and related complications. In addition, this review emphasizes the role of genome wide association studies and epigenetic factors. In the present review, we have identified some of the most significant protein encoding genes whose mutations have great impact in the development of diabetic condition. The characteristic features of these genes such as the risk level associated with the genes and inter-genic associations both in terms of position and functional proximity have been discussed. Additionally, genomic studies and epigenetic aspects have also been highlighted for wider comprehension of the diabetic condition from a genetic perspective. The present review would be of significance in prevention, screening, diagnosis, treatment and management of different forms of diabetes.

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