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Nov 11, 2017

International Diabetes Federation 2017 Congress

Genetic associations with diabetic retinopathy and coronary artery disease in Emirati patients with type-2 diabetes

;

Azzam, S.;

Osman, W.;

Lee, S.M.;

Khalaf, K.;

Khandoker, A.;

Almahmeed, W.;

Jelinek, H.;

Alsafar, H.

Abstract

Abstract

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Keywords

Abstract

Background: Diabetes is one of the largest health emergencies globally, where the International Diabetes Federation (IDF) reported that 415 million people have been diagnosed with diabetes in 2015, and the number is expected to rise to 642 million by 2040. In the United Arab Emirates (UAE), diabetes prevalence in adults between the ages of 20 to 79 years old, was found to be 19.3% in 2015. Type 2 diabetes mellitus (T2DM) accounts for more than 90% of patients diagnosed with diabetes; characterizing T2DM as the most common type of diabetes. Aims: Long-term debilitating complications and health issues are consequent events to T2DM. Microvascular complications such as diabetic retinopathy (DR), and macrovascular complications such as coronary artery disease (CAD), are examples of T2DM-associated complications. The development of these two complications is affected by genetic risk factors. A case-control study was performed, focusing on investigating genetic variations in association with DR and CAD, in T2DM patients from the United Arab Emirates. Methods: A total of four-hundred and seven Emirati patients with T2DM were recruited into the current study. Study population was categorized based on the presence or absence of DR and CAD. For association analyses, we selected seventeen Single Nucleotide Polymorphisms (SNPs) that were reported in previous studies. In evaluating the association between the seventeen SNPs and DR, CAD, or both complications, a multivariate logistic regression test was conducted, with a significance level set at p< 0.05. Results and Discussion: The SNPs rs9362054 near the CEP162 (centrosomal protein 162) gene and rs4462262 near the UBE2D1 (ubiquitin conjugating enzyme E2 D1) gene were significantly associated with DR (OR=1.73, p =0.00029; OR= 1.33, p = 0.045; respectively), and rs12219125 nearby the PLXDC2 (Plexin domain-containing protein 2) gene was significantly associated with CAD (OR= 2.26, p= 0.034). Moreover, rs9362054 nearby the CEP162 gene was significantly associated with both complications (OR= 2.26, p = 0.0020). Of note is that KIAA0825 gene, a protein-coding gene with uncharacterized protein KIAA0825, might have a protective role either directly or in linkage with other genes. The susceptibility genes for CAD (PLXDC2) and DR (UBE2D1) have a role in angiogenesis and neovascularization. Moreover, association in terms of retinal neural processing was found between the ciliary gene CEP162 and DR, confirming previous reports. The current study reports significant associations of different genetic variations with DR and CAD. We report new associations between CAD and PLXDC2, and DR with UBE2D1 using data from patients diagnosed with T2DM from the UAE. References [1] “IDF Diabetes Atlas - 7th Edition,” International Diabetes Federation (IDF)-Diabetes Atlas 7th Edition 2015. [Online]. Available: http://www.diabetesatlas.org/. [Accessed: 15-Aug-2016]. [2] E. P. Widmaier, H. Raff, K. T. Strang, and A. J. Vander, “Vander’s human physiology: the mechanisms of body function,” in Vander’s human physiology: the mechanisms of body function, 12th ed., New York: McGraw-Hill, 2011, pp. 581–583.

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All rights reserved.