Genetics, Genomics and Personalized Medicine in Type 2 Diabetes: A Perspective on the Arab Region

Siddiqui, Khalid; Tyagi, Shivani

doi:10.2217/pme.15.11

Cited by 5 publications

(6 citation statements)

References 102 publications

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“…A genome wide association study entails high density sampling of common human gene variation. Large-scale GWAS analyses in case of familial inheritance have facilitated for the identification of numerous genetic variants conferring threat to diabetes [18]. Hence, GWAS studies are boundless having ample facts of particular genes and the prospective to ascertain biological effects of genes [123–125].…”

Section: Genome Wide Association Studies (Gwas)mentioning

confidence: 99%

“…In case of T2D leading to DR, the implications have been insightful as the polymorphism discovery in the HLA region accounts for only 5–10% of disease heritability [126] which states a large constituent of genetic predisposition to T2D, that still requires an identification portfolio. This reflection suggests that environmental or epigenetic factors might influence the disease predisposition [18] and its inclination towards the triggered metabolic and signaling pathways. The initial linkage studies in T2D affected families (further leading to DR) identified CAPN10 and TCF7L2 as risk-conferring genes [127].…”

Section: Genome Wide Association Studies (Gwas)mentioning

confidence: 99%

“…Third, next generation DNA/RNA sequencing (NGS) may provide assistance by identifying exceptional genetic variants having the significant effects on T1D and T2D sufferers that could aid in the early detection of diabetic complications [18]. Epigenomics, transcriptomics, proteomics, metabolomics and systems biology are also rapidly developing techniques that are fitted inside the personalized or precision medicine toolbox.…”

Section: Future Prospectsmentioning

confidence: 99%

“…Factors influencing the treatment goals and strategies include age, gender, diabetes duration, epigenetics, diabetic complications and the presence of comorbidities (cardiovascular diseases, obesity, etc.). For instance, treatment varies from individual to individual, the treatment plan for an individual with an early onset of diabetic complications, who is actually at an increased risk will vary from the patient having late onset of the disease due to prolonged exposure to hyperglycemic conditions [18,157]. …”

Section: Future Prospectsmentioning

confidence: 99%

“…According to the statistics of International Federation of Diabetes (IFD) [17,18] more than 382 million people were affected with diabetes in the year 2013, and the remaining were left undiagnosed. It has also being estimated that the number of cases is expected to rise to 592 million till 2035, this will thus suppress the health, life span and productivity of an individual.…”

Section: Introductionmentioning

confidence: 99%

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Genetic and epigenetic modifications in the pathogenesis of diabetic retinopathy: a molecular link to regulate gene expression

Pradhan¹,

Upadhyay²,

Tiwari³

et al. 2016

New Front Ophthalmol

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Intensification in the frequency of diabetes and the associated vascular complications has been a root cause of blindness and visual impairment worldwide. One such vascular complication which has been the prominent cause of blindness; retinal vasculature, neuronal and glial abnormalities is diabetic retinopathy (DR), a chronic complicated outcome of Type 1 and Type 2 diabetes. It has also become clear that “genetic” variations in population alone can’t explain the development and progression of diabetes and its complications including DR. DR experiences engagement of foremost mediators of diabetes such as hyperglycemia, oxidant stress, and inflammatory factors that lead to the dysregulation of “epigenetic” mechanisms involving histone acetylation and histone and DNA methylation, chromatin remodeling and expression of a complex set of stress-regulated and disease-associated genes. In addition, both elevated glucose concentration and insulin resistance leave a robust effect on epigenetic reprogramming of the endothelial cells too, since endothelium associated with the eye aids in maintaining the vascular homeostasis. Furthermore, several studies conducted on the disease suggest that the modifications of the epigenome might be the fundamental mechanism(s) for the proposed metabolic memory’ resulting into prolonged gene expression for inflammation and cellular dysfunction even after attaining the glycemic control in diabetics. Henceforth, the present review focuses on the aspects of genetic and epigenetic alterations in genes such as vascular endothelial growth factor and aldose reductase considered being associated with DR. In addition, we discuss briefly the role of the thioredoxin-interacting protein TXNIP, which is strongly induced by high glucose and diabetes, in cellular oxidative stress and mitochondrial dysfunction potentially leading to chromatin remodeling and ocular complications of diabetes. The identification of disease-associated genes and their epigenetic regulations will lead to potential new drugs and gene therapies as well as personalized medicine to prevent or slow down the progression of DR.

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Section: Genome Wide Association Studies (Gwas)mentioning

confidence: 99%