Prognostic value of T786C and G894T eNOS polymorphisms in sickle cell disease

Armenis, Iakovos; Kalotychou, Vassiliki; Tzanetea, Revekka; Κollia, Panagoula; Kontogeorgiou, Zoi; Anastasopoulou, Dimitra; Mantzourani, Marina; Samarkos, Michael; Pantos, Konstantinos; Konstantopoulos, Kostas; Rombos, Ioannis

doi:10.1016/j.niox.2016.11.002

Cited by 12 publications

(6 citation statements)

References 42 publications

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“…On the other hand, the NOS3 rs1799983_T allele, which leads to aspartate for glutamate substitution at eNOS position 298, has been previously reported to be related to deficient eNOS caveolar localization and deficient shear stress response leading to reduced enzymatic activity. This SNP has been found in some populations to be more prevalent in patients with coronary artery disease, ischemic stroke and arterial hypertension [27]. However, in our study population, we did not observe any relationship of rs1799983 TT or GT genotypes with CV, biochemical or hematological parameters.…”

Section: Discussioncontrasting

confidence: 83%

Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia

Silva

Vargas

Coelho

et al. 2020

Blood Cells, Molecules, and Diseases

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We investigated biomarkers and genetic modulators of the cerebral vasculopathy (CV) subphenotype in pediatric sickle cell anemia (SCA) patients of sub-Saharan African ancestry. We found that one VCAM1 promoter haplotype (haplotype 7) and VCAM1 single nucleotide variant rs1409419_T were associated with stroke events, stroke risk, as measured by time-averaged mean of maximum velocity in the middle cerebral artery, and with high serum levels of the hemolysis biomarker lactate dehydrogenase. Furthermore, VCAM-1 ligand coding gene ITGA4 variants rs113276800_A and rs3770138_T showed a positive association with stroke events. An additional positive relationship between a genetic variant and stroke risk was observed for ENPP1 rs1044498_A. Conversely, NOS3 variants were negatively associated with silent cerebral infarct events (VNTR 4b_allele and haplotype V) and CV globally (haplotype VII). The -alpha 3.7kb -thal deletion did not show association with CV. However, it was associated with higher red blood cell and neutrophil counts, and lower mean corpuscular volume, mean corpuscular hemoglobin and red cell distribution width.Our results underline the importance of genetic modulators of the CV sub-phenotype and their potential as SCA therapeutic targets. We also propose that a biomarker panel comprising biochemical, hematological, imaging and genetic data would be instrumental for CV prediction, and prevention.

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Section: Discussioncontrasting

confidence: 83%

Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia

Silva

Vargas

Coelho

et al. 2020

Blood Cells, Molecules, and Diseases

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“… 74 In another study that aimed to determine endothelial NO synthase genotype for T786C and G894T polymorphisms, the 786CC genotype was more common in SS and Sβ 0 Greek patients with retinopathy. 75 Moreover, 894TT SS and Sβ 0 patients tended to have a higher hematocrit value than 894GG and GT ones, suggesting that they could be predisposed to higher risk of retinopathy. 75 Nevertheless, there is still a paucity of reports and a lack of GWAS regarding genetic modifiers specifically involved in SCR phenotypes.…”

Section: Clinical Systemic and Genetic Risk Factors Of Scrmentioning

confidence: 97%

“… 75 Moreover, 894TT SS and Sβ 0 patients tended to have a higher hematocrit value than 894GG and GT ones, suggesting that they could be predisposed to higher risk of retinopathy. 75 Nevertheless, there is still a paucity of reports and a lack of GWAS regarding genetic modifiers specifically involved in SCR phenotypes. In addition to genetic modifiers, one should remember that other contributors could be significantly involved in the etiology of the heterogeneous SCD and SCR phenotypes (eg, environmental components, genetic background of the population, socioeconomics, and psychology).…”

Section: Clinical Systemic and Genetic Risk Factors Of Scrmentioning

confidence: 97%

Sickle cell retinopathy: improving care with a multidisciplinary approach

Menaa¹,

Khan²,

Uzair³

et al. 2017

JMDH

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Sickle cell retinopathy (SCR) is the most representative ophthalmologic complication of sickle cell disease (SCD), a hemoglobinopathy affecting both adults and children. SCR presents a wide spectrum of manifestations and may even lead to irreversible vision loss if not properly diagnosed and treated at the earliest. Over the past decade, multidisciplinary research developments have focused upon systemic, genetic, and ocular risk factors of SCR, enabling the clinician to better diagnose and manage these patients. In addition, newer imaging and testing modalities, such as spectral domain-optical coherence tomography angiography, have resulted in the detection of subclinical retinopathy related to SCD. Innovative therapy includes intravitreal injection of an anti-vascular endothelial growth factor (eg, Lucentis® [ranibizumab] or Eylea® [aflibercept]) which appears comparatively safe and efficient, and may be combined with laser photocoagulation (LPC) for proliferative SCR. The effect of LPC alone does not significantly lead to the regression of advanced SCR, although it helps in avoiding hemorrhage and sight loss. This comprehensive article is based on 10-years retrospective (2007–2017) studies. It aims to present advances and recommendations in SCR theranostics while pointing out the requirement of combinatorial approaches for better management of SCR patients. To reach this goal, we identified and analyzed randomized original and review articles, clinical trials, non-randomized intervention studies, and observational studies using specified keywords in various databases (eg, Medline, Embase, Cochrane, ClinicalTrials.gov).

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“…A crosssectional study in a Brazilian SCA cohort showed that IL-6-597G>A is associated with a higher likelihood of retinopathy [34]. A Greek study determined that the endothelial nitric oxide (NO) synthase T786C polymorphism was more common in HbSS and HbSβ0 patients with retinopathy in comparison with the G894T polymorphism [35]. Environmental factors may confound these studies.…”

Section: Genetic and Systemic Risk Factors Of Sickle Cell Retinopathymentioning

confidence: 99%

Sickle cell retinopathy. A focused review

Elsayed

Mura

Dhibi

et al. 2019

Graefes Arch Clin Exp Ophthalmol

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Purpose To provide a focused review of sickle cell retinopathy in the light of recent advances in the pathogenesis, multimodal retinal imaging, management of the condition, and migration trends, which may lead to increased prevalence of the condition in the Western world. Methods Non-systematic focused literature review. Results Sickle retinopathy results from aggregation of abnormal hemoglobin in the red blood cells in the retinal microcirculation, leading to reduced deformability of the red blood cells, stagnant blood flow in the retinal precapillary arterioles, thrombosis, and ischemia. This may be precipitated by hypoxia, acidosis, and hyperosmolarity. Sickle retinopathy may result in sight threatening complications, such as paracentral middle maculopathy or sequelae of proliferative retinopathy, such as vitreous hemorrhage and retinal detachment. New imaging modalities, such as wide-field imaging and optical coherence tomography angiography, have revealed the microstructural features of sickle retinopathy, enabling earlier diagnosis. The vascular growth factor ANGPTL-4 has recently been identified as a potential mediator of progression to proliferative retinopathy and may represent a possible therapeutic target. Laser therapy should be considered for proliferative retinopathy in order to prevent visual loss; however, the evidence is not very strong. With recent development of wide-field imaging, targeted laser to ischemic retina may prove to be beneficial. Exact control of intraoperative intraocular pressure, including valved trocar vitrectomy systems, may improve the outcomes of vitreoretinal surgery for complications, such as vitreous hemorrhage and retinal detachment. Stem cell transplantation and gene therapy are potentially curative treatments, which may prevent retinopathy. Conclusions There is lack of evidence regarding the optimal management of sickle retinopathy. Further study is needed to determine if recent progress in the understanding of the pathophysiology and diagnosis of sickle retinopathy may translate into improved management and outcome.

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Prognostic value of T786C and G894T eNOS polymorphisms in sickle cell disease

Cited by 12 publications

References 42 publications

Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia

Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia

Sickle cell retinopathy: improving care with a multidisciplinary approach

Sickle cell retinopathy. A focused review

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