The A445C Variant in Apelin Receptor and Diabetic Retinopathy in Tunisian Patients

Soualmia, Hayet; Midani, Fatma; Hadj-Fradj, Sondess; Saadi, Nedra; Lassoued, Mehdi Ben; T, Messoud; Gharbi, M.; Ben-Amor, Zohra

doi:10.7754/clin.lab.2016.160424

Cited by 3 publications

(4 citation statements)

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“…However, they found that carriers of the CC (GG) genotype had greater weights and higher systolic and diastolic blood pressures. Soualmia et al (2017) in a Tunisian population found no association with diabetic retinopathy but found that CC (GG) bearers had higher total cholesterol levels than those with the AA (TT) genotype. These studies suggest that although the C (G) allele may not be able to predict disease in these populations, it could contribute to risk factors for cardiovascular disease.…”

Section: Human Polymorphismsmentioning

confidence: 89%

International Union of Basic and Clinical Pharmacology. CVII. Structure and Pharmacology of the Apelin Receptor with a Recommendation that Elabela/Toddler Is a Second Endogenous Peptide Ligand

Read¹,

Nyimanu²,

Williams³

et al. 2019

Pharmacol Rev

106

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The predicted protein encoded by the APJ gene discovered in 1993 was originally classified as a class A G protein-coupled orphan receptor but was subsequently paired with a novel peptide ligand, apelin-36 in 1998. Substantial research identified a family of shorter peptides activating the apelin receptor, including apelin-17, apelin-13, and [Pyr 1 ]apelin-13, with the latter peptide predominating in human plasma and cardiovascular system. A range of pharmacological tools have been developed, including radiolabeled ligands, analogs with improved plasma stability, peptides, and small molecules including biased agonists and antagonists, leading to the recommendation that the APJ gene be renamed APLNR and encode the apelin receptor protein. Recently, a second endogenous ligand has been identified and called Elabela/Toddler, a 54amino acid peptide originally identified in the genomes of fish and humans but misclassified as noncoding. This precursor is also able to be cleaved to shorter sequences (32, 21, and 11 amino acids), and all are able to activate the apelin receptor and are blocked by apelin receptor antagonists. This review summarizes the pharmacology of these ligands and the apelin receptor, highlights the emerging physiologic and pathophysiological roles in a number of diseases, and recommends that Elabela/Toddler is a second endogenous peptide ligand of the apelin receptor protein. 468 Read et al. Receptor residues implicated in apelin binding by mutagenesis. b Receptor residues affecting bias and internalization by mutagenesis. 470 Read et al.

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Section: Human Polymorphismsmentioning

confidence: 89%

International Union of Basic and Clinical Pharmacology. CVII. Structure and Pharmacology of the Apelin Receptor with a Recommendation that Elabela/Toddler Is a Second Endogenous Peptide Ligand

Read¹,

Nyimanu²,

Williams³

et al. 2019

Pharmacol Rev

106

View full text Add to dashboard Cite

show abstract

“…As a fat cytokine, Apelin plays an important role in various pathophysiological processes such as inflammatory response, immune response, cell growth and development, and apoptosis [ 16 , 31 ]. Recent studies have found that apelin can stimulate retinal endothelial cell proliferation and retinal neovascularization [ 32 – 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…Apelin is a new type of adipokine, it’s also a kind of angiotensin receptor-related protein [ 15 ]. It’s been reported that Apelin is involved in the proliferation of retinal endothelial cells and the angiogenesis process [ 16 ]. Furthermore, previous studies have reported that heme oxygenase 1 (HO-1) abnormally expressed in retinal cells cultured in high glucose and in the retina of diabetes animal models [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

VEGF, apelin and HO-1 in diabetic patients with retinopathy: a correlation analysis

Zhu

Zhou

2020

BMC Ophthalmol

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Background: It's necessary to analyze the role of VEGF, apelin, and HO-1 in patients with type 2 diabetes (T2DM), and to evaluate its relevance to diabetic retinopathy (DR). Methods: T2DM patients who were treated in our hospital from December 1, 2018 to November 30, 2019 were included. T2DM patients were divided into non-DR (NDR) group, non-proliferative DR (NPDR) group, and proliferative DR (PDR) group. and healthy participants were selected as the control group. The value of VEGF, apelin, and HO1 in predicting PDR were analyzed by receiver operating characteristic (ROC) curve, and the relations of VEGF, apelin, HO-1 and clinical factors in PDR patients were analyzed by Pearson correlation analysis. Results: A total of 295 participants were included. The level of FPG and HbAlc in PDR group were significantly higher than that of other groups (all p < 0.05); the level of VEGF and apelin in PDR group were significantly higher than that of other groups (all p < 0.05), but the level of HO-1 in PDR group were significantly less than that of other groups(p = 0.017); the AUC of VEGF, apelin, HO-1 and combined use was 0.806(95%CI: 0.779-0.861), 0.819(95%CI: 0.765-0.878), 0.808(95%CI: 0.733-0.869) and 0.902(95%CI: 0.822-0.958) respectively, the AUC, sensitivity, specificity of the three combined use was significantly higher than that of single VEGF, apelin, HO-1 use(all p < 0.05). The cutoff values of serum VEGF, apelin, and HO-1 levels for predicting PDR were 163.85 pg/ml, 8.27 ng/ml, and 26.06 mmol/L respectively. Serum VEGF, apelin, and HO-1 in patients with PDR was related to the time course of DM, FPG and HbAlc (all p < 0.05). Conclusions: VEGF, apelin and HO-1 are related to the progress of DR, and the combined use of VEGF, apelin and HO-1 is beneficial to the diagnosis and treatment of PDR.

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“…Soualmia et al. () performed a study on a small cohort of Tunisian patients analysing one SNP in APLNR (rs376527330), and they did not find any association between the APLNR polymorphism and DR.…”

Section: Chronic Hyperglycaemiamentioning

confidence: 99%

Diabetic macular oedema: under‐represented in the genetic analysis of diabetic retinopathy

Broadgate

Kiire

Halford

et al. 2018

Acta Ophthalmologica

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Diabetic retinopathy, a complication of both type 1 and type 2 diabetes, is a complex disease and is one of the leading causes of blindness in adults worldwide. It can be divided into distinct subclasses, one of which is diabetic macular oedema. Diabetic macular oedema can occur at any time in diabetic retinopathy and is the most common cause of vision loss in patients with type 2 diabetes. The purpose of this review is to summarize the large number of genetic association studies that have been performed in cohorts of patients with type 2 diabetes and published in English-language journals up to February 2017. Many of these studies have produced positive associations with gene polymorphisms and diabetic retinopathy. However, this review highlights that within this large body of work, studies specifically addressing a genetic association with diabetic macular oedema, although present, are vastly under-represented. We also highlight that many of the studies have small patient numbers and that meta-analyses often inappropriately combine patient data sets. We conclude that there will continue to be conflicting results and no meaningful findings will be achieved if the historical approach of combining all diabetic retinopathy disease states within patient cohorts continues in future studies. This review also identifies several genes that would be interesting to analyse in large, well-defined cohorts of patients with diabetic macular oedema in future candidate gene association studies.

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The A445C Variant in Apelin Receptor and Diabetic Retinopathy in Tunisian Patients

Abstract: The APLNR A445C polymorphism was not associated with DR in a sample of the Tunisian population, but the CC genotype carrier patients with DR had a high TC concentration.

Cited by 3 publications

References 0 publications

International Union of Basic and Clinical Pharmacology. CVII. Structure and Pharmacology of the Apelin Receptor with a Recommendation that Elabela/Toddler Is a Second Endogenous Peptide Ligand

International Union of Basic and Clinical Pharmacology. CVII. Structure and Pharmacology of the Apelin Receptor with a Recommendation that Elabela/Toddler Is a Second Endogenous Peptide Ligand

VEGF, apelin and HO-1 in diabetic patients with retinopathy: a correlation analysis

Diabetic macular oedema: under‐represented in the genetic analysis of diabetic retinopathy

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