Genetic Variants and Their Associations to Type 2 Diabetes Mellitus Complications in the United Arab Emirates

Abstract

AimType 2 Diabetes Mellitus (T2DM) is associated with microvascular complications, including diabetic retinopathy (DR), diabetic nephropathy (DNp), and diabetic peripheral neuropathy (DPN). In this study, we investigated genetic variations and Single Nucleotide Polymorphisms (SNPs) associated with DR, DNp, DPN and their combinations among T2DM patients of Arab origin from the United Arab Emirates, to establish the role of genes in the progression of microvascular diabetes complications.MethodsA total of 158 Emirati patients with T2DM were recruited in this study. The study population was divided into 8 groups based on the presence of single, dual, or all three complications. SNPs were selected for association analyses through a search of publicly available databases, specifically genome-wide association study (GWAS) catalog, infinome genome interpretation platform, and GWAS Central database. A multivariate logistic regression analysis and association test were performed to evaluate the association between 83 SNPs and DR, DNp, DPN, and their combinations.ResultsEighty-three SNPs were identified as being associated with T2DM and 18 SNPs had significant associations to one or more diabetes complications. The most strongly significant association for DR was rs3024997 SNP in the VEGFA gene. The top-ranked SNP for DPN was rs4496877 in the NOS3 gene. A trend towards association was detected at rs833068 and rs3024998 in the VEGFA gene with DR and rs743507 and rs1808593 in the NOS3 gene with DNp. For dual complications, the rs833061, rs833068 and rs3024997 in the VEGFA gene and the rs4149263 SNP in the ABCA1 gene were also with borderline association with DR/DNp and DPN/DNp, respectively. Diabetic with all of the complications was significantly associated with rs2230806 in the ABCA1 gene. In addition, the highly associated SNPs rs3024997 of the VEGFA gene and rs4496877 of the NOS3 gene were linked to DR and DPN after adjusting for the effects of other associated markers, respectively.ConclusionsThe present study reports associations of different genetic polymorphisms with microvascular complications and their combinations in Emirati T2DM patients, reporting new associations, and corroborating previous findings. Of interest is that some SNPs/genes were only present if multiple comorbidities were present and not associated with any single complication.

Whole‐genome sequencing study to identify candidate markers indicating susceptibility to type 2 diabetes in Bama miniature pigs

“…3 Natural genetic variation analysis has also been used to explore the mechanism of diabetes and its complications and predict the disease risk. [4][5][6][7] An ideal T2DM animal model is an essential tool for studying the pathogenesis of diabetes and developing new drugs. The minipig T2DM model can simulate the pathogenesis of human T2DM better than other current models.…”

“…With the development of genome‐wide association studies (GWAS) and single‐nucleotide polymorphism (SNP) analysis technology, hundreds of single‐nucleotide polymorphism (SNP) loci have been found to be closely related to human T2DM 3 . Natural genetic variation analysis has also been used to explore the mechanism of diabetes and its complications and predict the disease risk 4–7 …”

Decreased Alu methylation in type 2 diabetes mellitus patients increases HbA1c levels

“…Type 2 DM patients can develop various complications, including cardiovascular disease, stroke, foot ulcers, chronic kidney failure, and diabetic retinopathy, 3–10 making it one of the world's most critical health concerns 11,12 . Type 2 DM is a multifactorial condition characterized by high blood glucose levels (hyperglycemia), 13–15 which are influenced by genetic and epigenetic factors 16–19 . DNA methylation, an epigenetic event commonly found in elderly individuals, exhibits changes in type 2 DM patients and correlates with poor health status in humans 20–27 …”

“…11,12 Type 2 DM is a multifactorial condition characterized by high blood glucose levels (hyperglycemia), [13][14][15] which are influenced by genetic and epigenetic factors. [16][17][18][19] DNA methylation, an epigenetic event commonly found in elderly individuals, exhibits changes in type 2 DM patients and correlates with poor health status in humans. [20][21][22][23][24][25][26][27] DNA methylation serves two fundamental purposes: genomic stability prevention and gene expression regulation.…”

Identification of Potential EGFR Inhibitors for Type 2 Diabetes and Pancreatic Cancer Treatment: A Computational Approach

“…T hese cells are responsible for secreting hormones such as insulin, glucagon, and so-matostatin, among others, as well as altered functionality of these cells [7], leading to insufficient in-sulin release and eventually hyperglycemia. Several genetic variants [8, 9, 10], identified through genome-wide association studies ( GWAS ), have been associated with the risk of developing T2D by influencing beta-cell function, mass, or response to various stimuli. O verall, the association between T2D and pancreatic islets highlights the importance of studying the underlying molecular mechanisms involved in the pathophysiology of disease onset and progression.…”