Role of engulfment and cell motility 1 (ELMO1) gene polymorphism in development of diabetic kidney disease

Omar, Thoria Ahmed; Zewain, Shimaa Kamal; Ghonaim, Mohamed; Refaat, Khadija A.; Abou-Elela, Dalia H

doi:10.1186/s43042-021-00167-8

Cited by 8 publications

(7 citation statements)

References 36 publications

(45 reference statements)

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“…Serum level of VEGF-A was significantly increased in T2DM patients with mixed microvascular complications in comparison with the control group. This result was confirmed by Mahdy et al [25] who found a considerable rise in serum VEGF in diabetic patients with various micro-and macrovascular complications compared to the uncomplicated diabetic patients and control subjects. Biswas et al [26] discovered that elevated VEGF-A level was a risk factor for the presence and severity of vascular complications in diabetic patients, and VEGF-A concentrations tend to increase with the progression of mixed diabetic microvascular complications.…”

Section: Parameterssupporting

confidence: 68%

Vascular endothelial growth factor A with two genetic variants for prediction of mixed microvascular diabetic complications

Omar

El-Saeed

Khodeer

et al. 2022

Egypt J Med Hum Genet

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Background Vascular endothelial growth factor (VEGF) is a signal protein, induces cell proliferation, and enhances the permeability of the endothelial cells. VEGF-A gene is highly polymorphic, with different near-gene variants at varied frequencies linked with altered VEGF protein expression, type 2 diabetes mellitus (T2DM) susceptibility, and associated microvascular complications. The present study aimed to investigate the role of two genetic variants of VEGF-A, − 583C > T (rs3025020) and + 936 C/T (rs3025039), for predicting mixed microvascular complications in T2DM. This case–control study was performed on 26 T2DM patients with mixed microvascular complications and 26 apparently healthy individuals, as a control group. Clinical, neurological, funds examinations, and biochemical laboratory investigations were conducted on all groups. The serum level of VEGF-A was measured using ELISA. Genotyping of VEGF-A was performed by real-time PCR allelic discrimination system. Results Serum level of VEGF-A was significantly increased in T2DM with mixed complications. T allele of VEGF-A rs3025020 showed higher frequency among T2DM patients with mixed complications than in control group [OR 2.67; 95% CI 1.03–6.91; p = 0.04], while CT genotype and T allele of VEGF-A rs3025039 had a high frequency in mixed complication group [OR 4.08; 95% CI 1.32–17.44; p = 0.01 and OR 4.02; 95% CI 1.52–10.63; p = 0.004, respectively]. Conclusion VEGF-A increased the level contributed in the pathogenesis of mixed diabetic microvascular complications. T allele of VEGF-A rs3025020, CT genotype, and T allele of VEGF-A rs3025039 had the highest frequency in mixed diabetic microvascular complications, so they were considered risk genes for mixed diabetic microvascular complications.

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Section: Parameterssupporting

confidence: 68%

Vascular endothelial growth factor A with two genetic variants for prediction of mixed microvascular diabetic complications

Omar

El-Saeed

Khodeer

et al. 2022

Egypt J Med Hum Genet

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“…This systematic review finally included 17 studies, of which 15 studies were eligible and included in meta-analysis and the other two studies were excluded due to lack of data (Fig 1). Twelve studies followed a case-control design [4,11,[25][26][27][28][29][30][31][32][33][34] while the other 5 were genomewide association studies [7,[35][36][37][38], with a total of 5794 DM with DKD patients, 4886 DM without DKD patients, and 2023 healthy controls to assess the impact of ELMO1 polymorphism on DKD susceptibility. Most studies included patients with T2DM, except for two studies with T1DM patients [7,36].…”

Section: Study Characteristics and Demographymentioning

confidence: 99%

“…Studies were sub-grouped based on their geographical region; Middle East [25,28,29,32,37], South Asia [26,31,33,35], East Asia [4,11,30,33,38], Europe [34], and USA [7,27,36].…”

Section: Study Characteristics and Demographymentioning

confidence: 99%

“…When failing to do so, analyses of Galbraith plot were used to investigate the sources of heterogeneity (Fig 4). In rs741301 under allele model in DM vs. healthy control, when Omar 2021 [29] was omitted, heterogeneity significantly decreased (I 2 = 0%; P = 0.84). Hou 2019 [38], Bodhini 2016 [35], and Wu 2013 [30] Risk of bias and publication bias.…”

Section: Study Characteristics and Demographymentioning

confidence: 99%

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Association between ELMO1 gene polymorphisms and diabetic kidney disease: A systematic review and meta-analysis

Azarboo,

Hosseinkhani,

Ghaseminejad-Raeini

et al. 2024

PLoS ONE

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Background Previous research has suggested that the ELMO1 gene may play a role in the development of diabetic kidney disease. Diabetic kidney disease (DKD) is a serious complication of diabetes and the leading cause of chronic kidney disease and end-stage renal disease (ESRD). Objective and rationale This study aim was to systematically review and explore the association between ELMO1 gene polymorphisms and diabetic kidney disease. A comprehensive systematic review provides a clear conclusion and high-level evidence for the association between ELMO1 gene and DKD for future application in personalized medicine. Methods A comprehensive search of electronic databases, per PRISMA instructions, was conducted in Scopus, EMBASE, Web of Science, and PubMed databases from 1980 to January 2023. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using appropriate models. Subgroup and sensitivity analyses were performed to explore potential sources of heterogeneity and assess the robustness of the findings. Results A total of 5794 diabetes patients with DKD, 4886 diabetes patients without DKD, and 2023 healthy controls were included in the 17 studies that made up this systematic review. In the investigation of DM (Diabetes Mellitus) with DKD vs. DM without DKD, the susceptibility for DKD for the EMLO1 rs741301 polymorphism indicated a significant difference under the dominant, homozygote, and recessive genetic models. The susceptibility for DKD for the EMLO1 rs1345365, rs10255208, and rs7782979 polymorphisms demonstrated a significant difference under the allele genetic models in the analysis of DM with DKD vs. DM without DKD groups. There was a considerable increase in DKD risk in the Middle East when the population was stratified by the region. Conclusion The findings of the meta-analysis show that there are a significant connection between the EMLO1 rs741301 polymorphism and DKD susceptibility in overall analyses; as well as rs1345365, rs10255208, and rs7782979 polymorphisms; especially in the Middle East region.

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“…Higher expression of this protein was suggested to result in aberrant regulation of the extracellular matrix and consequently lead to kidney damage [96]. Another study demonstrated the association between increased expression of ELMO1 and the enhanced production of extracellular protein, diminished cell adhesion, as well as the accelerated progression of T2DM glomerulosclerosis [97]. FKBP5 encodes a cytosolic chaperone FK506 binding protein 51 (FKBP5), which acts as a negative regulator of GR signaling [98].…”

Section: Othermentioning

confidence: 99%

Are Alterations in DNA Methylation Related to CKD Development?

Rysz

Franczyk

Rysz-Górzyńska

et al. 2022

IJMS

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The modifications in genomic DNA methylation are involved in the regulation of normal and pathological cellular processes. The epigenetic regulation stimulates biological plasticity as an adaptive response to variations in environmental factors. The role of epigenetic changes is vital for the development of some diseases, including atherogenesis, cancers, and chronic kidney disease (CKD). The results of studies presented in this review have suggested that altered DNA methylation can modulate the expression of pro-inflammatory and pro-fibrotic genes, as well those essential for kidney development and function, thus stimulating renal disease progression. Abnormally increased homocysteine, hypoxia, and inflammation have been suggested to alter epigenetic regulation of gene expression in CKD. Studies of renal samples have demonstrated the relationship between variations in DNA methylation and fibrosis and variations in estimated glomerular filtration rate (eGFR) in human CKD. The unravelling of the genetic–epigenetic profile would enhance our understanding of processes underlying the development of CKD. The understanding of multifaceted relationship between DNA methylation, genes expression, and disease development and progression could improve the ability to identify individuals at risk of CKD and enable the choice of appropriate disease management.

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Role of engulfment and cell motility 1 (ELMO1) gene polymorphism in development of diabetic kidney disease

Cited by 8 publications

References 36 publications

Vascular endothelial growth factor A with two genetic variants for prediction of mixed microvascular diabetic complications

Vascular endothelial growth factor A with two genetic variants for prediction of mixed microvascular diabetic complications

Association between ELMO1 gene polymorphisms and diabetic kidney disease: A systematic review and meta-analysis

Are Alterations in DNA Methylation Related to CKD Development?

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