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Genetic Associations With Diabetic Retinopathy and Coronary Artery Disease in Emirati Patients With Type-2 Diabetes Mellitus.

ABSTRACT: Aim: Type 2 Diabetes Mellitus (T2DM) is associated with both microvascular complications such as diabetic retinopathy (DR), and macrovascular complications like coronary artery disease (CAD). Genetic risk factors have a role in the development of these complications. In the present case-control study, we investigated genetic variations associated with DR and CAD in T2DM patients from the United Arab Emirates. Methods: A total of 407 Emirati patients with T2DM were recruited. Categorization of the study population was performed based on the presence or absence of DR and CAD. Seventeen Single Nucleotide Polymorphisms (SNPs), were selected for association analyses through search of publicly available databases, namely GWAS catalog, infinome genome interpretation platform and GWAS Central database. A multivariate logistic regression test was performed to evaluate the association between the 17 SNPs and DR, CAD, or both. To account for multiple testing, significance was set at p < 0.00294 using the Bonferroni correction. Results: The SNPs rs9362054 near the CEP162 gene and rs4462262 near the UBE2D1 gene were associated with DR (OR = 1.66, p = 0.001; OR = 1.37, p = 0.031; respectively), and rs12219125 near the PLXDC2 gene was associated (suggestive) with CAD (OR = 2.26, p = 0.034). Furthermore, rs9362054 near the CEP162 gene was significantly associated with both complications (OR = 2.27, p = 0.0021). The susceptibility genes for CAD (PLXDC2) and DR (UBE2D1) have a role in angiogenesis and neovascularization. Moreover, association between the ciliary gene CEP162 and DR was established in terms of retinal neural processing, confirming previous reports. Conclusions: The present study reports associations of different genetic loci with DR and CAD. We report new associations between CAD and PLXDC2, and DR with UBE2D1 using data from T2DM Emirati patients.

SUBMITTER: Azzam SK

PROVIDER: S-EPMC6509200 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Genetic Associations With Diabetic Retinopathy and Coronary Artery Disease in Emirati Patients With Type-2 Diabetes Mellitus.

Azzam Sarah K SK Osman Wael M WM Lee Sungmun S Khalaf Kinda K Khandoker Ahsan H AH Almahmeed Wael W Jelinek Herbert F HF Al Safar Habiba S HS

Frontiers in endocrinology 20190503

<b>Aim:</b> Type 2 Diabetes Mellitus (T2DM) is associated with both microvascular complications such as diabetic retinopathy (DR), and macrovascular complications like coronary artery disease (CAD). Genetic risk factors have a role in the development of these complications. In the present case-control study, we investigated genetic variations associated with DR and CAD in T2DM patients from the United Arab Emirates. <b>Methods:</b> A total of 407 Emirati patients with T2DM were recruited. Catego ...[more]

PMID: 31130920

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Project description:BackgroundThe proportion of patients with diabetic retinopathy (DR) has grown with increasing number of diabetes mellitus patients in the world. It is among the major causes of blindness worldwide. The main objective of this study was to identify contributing risk factors of DR among people with type II diabetes mellitus.MethodA sample of 191 people with type II diabetes mellitus was selected from the Black Lion Specialized Hospital diabetic unit from 1 March 2018 to 1 April 2018. A multivariate stochastic regression imputation technique was applied to impute the missing values. The response variable, DR is a categorical variable with two outcomes. Based on the relationship derived from the exploratory analysis, the odds of having DR were not necessarily linearly related to the continuous predictors for this sample of patients. Therefore, a semiparametric model was proposed to identify the risk factors of DR.ResultFrom the sample of 191 people with type II diabetes mellitus, 98 (51.3%) of them had DR. The results of semiparametric regression model revealed that being male, hypertension, insulin treatment, and frequency of clinical visits had a significant linear relationships with the odds of having DR. In addition, the log- odds of having DR has a significant nonlinear relation with the interaction of age by gender (for female patients), duration of diabetes, interaction of cholesterol level by gender (for female patients), haemoglobin A1c, and interaction of haemoglobin A1c by fasting blood glucose with degrees of freedom [Formula: see text], respectively. The interaction of age by gender and cholesterol level by gender appear non significant for male patients. The result from the interaction of haemoglobin A1c (HbA1c) by fasting blood glucose (FBG) showed that the risk of DR is high when the level of HbA1c and FBG were simultaneously high.ConclusionClinical variables related to people with type II diabetes mellitus were strong predictive factors of DR. Hence, health professionals should be cautious about the possible nonlinear effects of clinical variables, interaction of clinical variables, and interaction of clinical variables with sociodemographic variables on the log odds of having DR. Furthermore, to improve intervention strategies similar studies should be conducted across the country.

Project description:BackgroundDiabetic retinopathy (DR) is the primary oculopathy causing blindness in diabetic patients. Currently, there is increasing interest in the role of lipids in the development of diabetic retinopathy, but it remains controversial. Remnant cholesterol (RC) is an inexpensive and easily measurable lipid parameter; however, the relationship between RC and DR in type 2 diabetes mellitus (T2DM) has not been elucidated. This research investigates the relevance between RC levels and DR severity while building a risk prediction model about DR.MethodsIn this single-centre retrospective cross-sectional study. Each hospitalised T2DM patient had no oral lipid-lowering drugs in the past three months, and coronary angiography showed epicardial coronary artery stenosis of less than 50% and completed seven-field stereo photographs, fluorescein fundus angiography, and optical coherence tomography detection. The RC value is calculated according to the internationally recognised formula. Binary logistic regression was used to correct confounding factors, and the receiver operating characteristic (ROC) analysis was used to identify risk factors and assess the nomogram's diagnostic efficiency.ResultsA total of 456 T2DM patients were included in the study. The RC levels in the DR team was higher [0.74 (0.60-1.12) mmo/l vs 0.54 (0.31-0.83) mmol/l P < 0.001] in the non-DR team. After adjusting for confounding elements, RC levels are still associated with DR risk (OR = 5.623 95%CI: 2.996-10.556 P < 0.001). The ratio of DR in every stage (except mild non-proliferative diabetic retinopathy) and DME in the high RC level team were further increased compared to the low-level team (all P < 0.001). After ROC analysis, the overall risk of DR was predicted by a nomogram constructed for RC, diabetes duration, and the neutrophil-lymphocyte ratio as 0.758 (95%CI 0.714-0.802 P < 0.001).ConclusionsHigh RC levels may be a potential risk factor for diabetic retinopathy, and the nomogram does better predict DR. Despite these essential findings, the limitation of this study is that it is single-centred and small sample size analysis.

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Genetic Associations With Diabetic Retinopathy and Coronary Artery Disease in Emirati Patients With Type-2 Diabetes Mellitus.

Publications

Genetic Associations With Diabetic Retinopathy and Coronary Artery Disease in Emirati Patients With Type-2 Diabetes Mellitus.

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