<p>Type 2 Diabetes-Associated Genetic Polymorphisms as Potential Disease Predictors</p>

Abstract

Diabetes is a major cause of mortality worldwide. There are several types of diabetes, with type 2 diabetes mellitus (T2DM) being the most common. Many factors, including environmental and genetic factors, are involved in the etiology of the disease. Numerous studies have reported the role of genetic polymorphisms in the initiation and development of T2DM. While genome-wide association studies have identified around more than 200 susceptibility loci, it remains unclear whether these loci are correlated with the pathophysiology of the disease. The present review aimed to elucidate the potential genetic mechanisms underlying T2DM. We found that some genetic polymorphisms were related to T2DM, either in the form of single-nucleotide polymorphisms or direct amino acid changes in proteins. These polymorphisms are potential predictors for the management of T2DM.

<p>Association Metabolic Obesity Phenotypes with Cardiometabolic Index, Atherogenic Index of Plasma and Novel Anthropometric Indices: A Link of FTO-rs9939609 Polymorphism</p>

“…17 The genome-wide association studies (GWAS) for obesity detected strong association between the fat massand obesity-associated gene (FTO) with higher body mass index (BMI) and metabolically unhealthy state in individuals. 18,19 At FTO-rs9939609 SNP, carriers of risk genotype (AA) have a 2.02-fold higher risk for obesity and 1.17-fold higher risk for metabolic syndrome compared with non-risk genotype carriers. 20,21 However, in several studies, the association FTO with metabolic traits was entirely explained by the association with obesity.…”

Silencing of the tRNA Modification Enzyme Cdkal1 Effects Functional Insulin Synthesis in NIT-1 Cells: tRNALys3 Lacking ms2- (ms2t6A37) is Unable to Establish Sufficient Anticodon:Codon Interactions to Decode the Wobble Codon AAG

“…A fundamental genetic heterogeneity has been found in T2DM ( Mannino et al, 2019 ). Genome Wide Association Studies (GWAS) focused on the genetic heterogeneity have discovered a number of loci, KLF14, KCNQ1, DUSP9, FTO, HNF4A, IGFBP2, CDKN2A/B, TCF7L2, KCNJ11, antioxidant genes, DNAJC3, PGC-1α, ADIPOQ, CDKAL1, POMC, PPARγ2, and SLC30A8 , that could be potential predictors of the disease ( Cho et al, 2019 ; Witka et al, 2019 ). One among the loci, in particular, CDK5 regulatory subunit associated protein 1-like 1, cdkal1 , is intriguing as a locus remote from the insulin gene, and a tRNA modification enzyme.…”

The Pro12Ala polymorphism of PPARγ2 modulates beta cell function and failure to oral glucose‐lowering drugs in patients with type 2 diabetes

“…We focus on the Pro12Ala polymorphism of the peroxisome proliferator‐activated receptor γ2 (PPARγ2) gene. This is one the best‐replicated genetic risk factor for T2D 9 . PPARγ2 encodes for a transcription factors that belong to the family of nuclear receptors; it regulates several genes involved in carbohydrates and lipids metabolism, promotes adipocytes differentiation and fatty acids uptake and modulates insulin sensitivity.…”

“…PPARγ2 encodes for a transcription factors that belong to the family of nuclear receptors; it regulates several genes involved in carbohydrates and lipids metabolism, promotes adipocytes differentiation and fatty acids uptake and modulates insulin sensitivity. Multiple studies have reproducibly shown that the common Pro12Ala polymorphism is associated with greater insulin sensitivity and protection from development of T2D in the general population 9 . Apparently at variance with this evidence, prospective studies in people with disglycaemia have shown that the Ala12 variant is associated with a greater risk of transition from impaired glucose tolerance to diabetes 10‐12 .…”