A study of the role of GATA2 gene polymorphism in coronary artery disease risk traits

Muiya, Nzioka P.; Wakil, Salma M.; Al-Najai, Mohammed; Tahir, Asma; Baz, Batoul; Andres, Editha; Al-Boudari, Olyan M.; Tassan, Nada Al; Alshahid, Maie; Meyer, Brian F.; Dzimiri, Nduna

doi:10.1016/j.gene.2014.04.064

Cited by 39 publications

(31 citation statements)

References 27 publications

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“…One explanation for the divergence between Gata2 mRNA and protein levels could be differential posttranscriptional/ posttranslational regulation in distinct vascular beds; indeed, our earlier work documenting that miR-451 levels are elevated in primary embryonic BECs compared with LECs (3) provides one potential mechanism by which this could be accomplished. An important role for GATA2 in arteries may underlie the hemorrhagic phenotype of Gata2 ΔEC mice described by us and others, as well as the association of GATA2 SNPs in patients with early-onset coronary artery disease (9)(10)(11). Targeted mutation of gata2a in zebrafish has recently been demonstrated to result in defective morphogenesis of the dorsal aorta, resulting in arterial-venous shunts and suggesting that arterial defects could also contribute to the vascular phenotype observed in Gata2 ΔEC mice.…”

Section: Discussionmentioning

confidence: 71%

“…While several earlier studies implicated GATA2 in vascular development (5)(6)(7)(8), the lack of an obvious vascular phenotype in Gata2 -/-mice prior to their demise around E10.5 has precluded in depth analyses of Gata2 function in vasculogenesis and angiogenesis. SNPs in GATA2 have been associated with coronary artery disease (9)(10)(11), implying a role for GATA2 in arterial development, while ablation of gata2a in zebrafish affects morphogenesis of the dorsal aorta (12). Recent studies in which Gata2 was deleted in hematopoietic and endothelial cell compartments (13), or was disrupted due to mutation of an enhancer element important for endothelial Gata2 expression (14), suggested that Gata2 is important for vascular integrity and for efficient separation of the blood and lymphatic vascular networks (13,14).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

GATA2 is required for lymphatic vessel valve development and maintenance

Kazenwadel¹,

Betterman²,

Chong³

et al. 2015

J. Clin. Invest.

193

259

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

GATA2 is required for lymphatic vessel valve development and maintenance

Kazenwadel¹,

Betterman²,

Chong³

et al. 2015

J. Clin. Invest.

193

259

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“…In adipose tissue, GATA2 phosphorylation is critical for adipocyte maturation/inflammation45. However, the role of GATA2 in cardiovascular disease is still controversial464748, and the pathophysiological role of its SUMOylation is largely unknown. Our previous study revealed that GATA1, another major member of the GATA family, is dynamically regulated by SUMO modification during developmental erythropoiesis31.…”

Section: Discussionmentioning

confidence: 99%

The critical role of SENP1-mediated GATA2 deSUMOylation in promoting endothelial activation in graft arteriosclerosis

et al. 2017

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Data from clinical research and our previous study have suggested the potential involvement of SENP1, the major protease of post-translational SUMOylation, in cardiovascular disorders. Here, we investigate the role of SENP1-mediated SUMOylation in graft arteriosclerosis (GA), the major cause of allograft failure. We observe an endothelial-specific induction of SENP1 and GATA2 in clinical graft rejection specimens that show endothelial activation-mediated vascular remodelling. In mouse aorta transplantation GA models, endothelial-specific SENP1 knockout grafts demonstrate limited neointima formation with attenuated leukocyte recruitment, resulting from diminished induction of adhesion molecules in the graft endothelium due to increased GATA2 SUMOylation. Mechanistically, inflammation-induced SENP1 promotes the deSUMOylation of GATA2 and IκBα in endothelial cells, resulting in increased GATA2 stability, promoter-binding capability and NF-κB activity, which leads to augmented endothelial activation and inflammation. Therefore, upon inflammation, endothelial SENP1-mediated SUMOylation drives GA by regulating the synergistic effect of GATA2 and NF-κB and consequent endothelial dysfunction.

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“…CHD is a complex disease, involving interactions between environmental and genetic factors (Feng et al, 2014). Previous studies have found that single nucleotide polymorphisms (SNPs), important genomic elements, can affect an individual's genetic susceptibility to various diseases, including CHD Muiya et al, 2014;Wu et al, 2014;Yang et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Lack of an association between matrix metalloproteinase polymorphisms and coronary heart disease in a Han Chinese population

Cm¹,

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Coronary heart disease (CHD) has become a leading cause of human deaths worldwide. Recent studied showed that polymorphisms of the matrix metalloproteinase (MMP) genes played important roles in extracellular matrix remodeling and contribute to the pathogenesis of vascular diseases. Here, we investigated whether these MMP gene polymorphisms were associated with CHD in Han Chinese. Our case-control study was involved with 1509 unrelated individuals, 12255Matrix metalloproteinases and coronary heart disease ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 12254-12261 (2015) including 777 CHD cases and 732 controls. We selected a total of five polymorphisms whose genotypes were determined using Sequenom iPLEX technology. Our results showed there were no significant associations between the five MMP gene polymorphisms and CHD risk at either genotype or allele levels (P > 0.05). Further subgroup analyses by sex were also unable to reveal any significant association (P > 0.05).In conclusion, no significant associations were found between the five MMP gene polymorphisms and the risk of CHD in Han Chinese.

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A study of the role of GATA2 gene polymorphism in coronary artery disease risk traits

Cited by 39 publications

References 27 publications

GATA2 is required for lymphatic vessel valve development and maintenance

GATA2 is required for lymphatic vessel valve development and maintenance

The critical role of SENP1-mediated GATA2 deSUMOylation in promoting endothelial activation in graft arteriosclerosis

Lack of an association between matrix metalloproteinase polymorphisms and coronary heart disease in a Han Chinese population

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