Matrix Gla protein T-138C polymorphism is associated with carotid intima media thickness and predicts mortality in patients with diabetic nephropathy

Roumeliotis, Stefanos; Roumeliotis, Athanasios; Panagoutsos, Stylianos; Giannakopoulou, Efstathia; Παπάνας, Νικόλαος; Manolopoulos, Vangelis G.; Passadakis, Ploumis; Tavridou, Anna

doi:10.1016/j.jdiacomp.2017.06.012

Cited by 38 publications

(41 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Uremia is a state of enhanced oxidative stress (OS) and a subsequent heavy cardiovascular (CV) burden . OS in chronic kidney disease (CKD) results from increased production of prooxidant molecules such as reactive oxygen species (ROS) and nitric oxide (NO), insufficient clearance of oxidative products, and deficient antioxidant defense mechanisms .…”

Section: Introductionmentioning

confidence: 99%

“…Uremia is a state of enhanced oxidative stress (OS) and a subsequent heavy cardiovascular (CV) burden. 1 OS in chronic kidney disease (CKD) results from increased production of prooxidant molecules such as reactive oxygen species (ROS) and nitric oxide (NO), insufficient clearance of oxidative products, and deficient antioxidant defense mechanisms. 2 Accumulation of ROS and NO trigger the activation of inflammatory mediators and subsequently promotes oxidation and modification of lipids, proteins, carbohydrates, and nucleic acids-such as deoxyribonucleic acid-(DNA).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Oxidative stress in hemodialysis: Causative mechanisms, clinical implications, and possible therapeutic interventions

Liakopoulos

Roumeliotis

Zarogiannis

et al. 2018

Seminars in Dialysis

Self Cite

103

View full text Add to dashboard Cite

Oxidative stress (OS) is the result of prooxidant molecules overwhelming the antioxidant defense mechanisms. Hemodialysis (HD) constitutes a state of elevated inflammation and OS, due to loss of antioxidants during dialysis and activation of white blood cells triggering production of reactive oxygen species. Dialysis vintage, dialysis methods, and type and condition of vascular access, biocompatibility of dialyzer membrane and dialysate, iron administration, and anemia all can play a role in aggravating OS, which in turn has been associated with increased morbidity and mortality. Oral or intravenous administration of antioxidants may detoxify the oxidative molecules and at least in part repair OS‐mediated tissue damage. Lifestyle interventions and optimization of a highly biocompatible HD procedure might ameliorate OS development in dialysis.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oxidative stress in hemodialysis: Causative mechanisms, clinical implications, and possible therapeutic interventions

Liakopoulos

Roumeliotis

Zarogiannis

et al. 2018

Seminars in Dialysis

Self Cite

103

View full text Add to dashboard Cite

show abstract

“…In the meantime, the study of Wang et al [24] is compatible to our results, hence, the rs4236 polymorphism found in association with higher MGP plasma levels and rs1800802 with lower levels. Even Farzaneh-Far et al [8] propounded that the rs1800802 CC allele has increased the transcriptional activity of the MGP gene, direct or inverse relationship of the rs4236 or rs1800802 polymorphism with serum/plasma MGP concentrations could not be established by certain investigations [14,25]. Furthermore, the association between serum MGP levels and CAD has not been verified in clinical investigations.…”

Section: Discussionmentioning

confidence: 99%

Association of genetic polymorphisms in the Matrix Gla Protein (MGP) gene with coronary artery disease and serum mgp levels

Karslı-Çeppioğlu

Yazar

Keskin

et al. 2019

Balkan Journal of Medical Genetics

View full text Add to dashboard Cite

Matrix Gla protein (MGP) is an important regulatory protein for inhibition of calcification in the vessel wall and cartilage. The MGP gene polymorphisms are suspected to increase the risk of extracellular calcification through altering the related gene expression and serum MGP levels. The goal of this study was to examine the correlation between rs4236 (Thr83-Ala), rs12304 (Glu60-X) and rs1800802 (T138-C) polymorphisms of the MGP gene and coronary artery calcification. Serum MGP levels of 168 subjects who had undergone coronary angiography were analyzed along with genotyping of MGP gene polymorphisms. The results indicated that serum MGP levels were significantly associated with rs4236 and rs1800802 polymorphisms of the MGP gene with the occurrence of coronary artery diseases (CAD). Allelic distributions of MGP gene polymorphisms and serum MGP levels, respectively, were not significantly interconnected with the presence of CAD. Our results revealed that serum MGP levels of CAD patients show association with rs4236 and rs1800802 polymorphisms, but serum MGP levels alone do not directly reflect the risk of CAD. The role of MGP genetic variants on formation and progression of arterial calcification should be regarded in cardiovascular diseases.

show abstract

“…Mutations leading to non-functional MGP expression have been repeatedly reported to be associated with Keutel syndrome, a rare condition characterized by excessive, ectopic calcification of soft tissues and cartilage (21). In a cohort of 118 patients with established diabetic nephropathy, followed for 7 years, MGP T-138C (rs rs1800802) polymorphism was found to be a strong, independent predictor of VC and CV mortality (22). Sheng et al, conducted a meta-analysis of 23 studies with 5,773 controls and 5,280 cases and found that MGP G-7A (rs1800801) polymorphism was an independent predictor of both intimal and medial calcification (23).…”

Section: Matrix Gla Protein: the Powerful Calcification Inhibitormentioning

confidence: 99%

“…The Maastricht group was the first to conduct a cross-sectional, prospective study in 107 uremic patients stratified in various stages of CKD (2-5) and found that circulating dp-ucMGP was strongly associated with aortic calcification score, deterioration of renal function and allcause mortality (32). In a cohort of 67 patients with diabetic CKD in stages 2-5, d-pucMGP was gradually increased with disease progression to ESRD and strongly predicted all-cause and CV mortality (22). Similarly, in CKD populations, several investigators reported a tight association between circulating dp-ucMGP and various VC markers and renal function (29,46,47).…”

Section: Matrix Gla Protein: the Powerful Calcification Inhibitormentioning

confidence: 99%

Vascular Calcification in Chronic Kidney Disease: The Role of Vitamin K- Dependent Matrix Gla Protein

et al. 2020

Self Cite

View full text Add to dashboard Cite

Arterial calcification is highly prevalent in chronic kidney disease (CKD) patients and is associated with cardiovascular (CV) morbidity and mortality. Patients at early CKD stages are more likely to suffer a fatal CV event than to develop end-stage renal disease and require hemodialysis treatment. The heavy CV burden of these patients cannot be solely explained by traditional calcification risk factors. Moreover, the pathophysiologic mechanisms underlying this association are complex and yet not fully understood. Although vascular calcification was regarded as a passive degenerative process for over a century, this theory changed by recent evidence that pointed toward an active process, where calcification promoters and inhibitors were involved. Matrix Gla Protein (MGP) has been established as a strong inhibitor of calcification both in vitro and in vivo. Not only it prevents mineralization of the arterial wall, but it is the only factor that can actually reverse it. To become fully active, MGP must undergo carboxylation of specific protein bound glutamate residues, a process fully dependent on the availability of vitamin K. Low vitamin K status leads to inactive, uncarboxylated forms of MGP and has been repeatedly associated with accelerated vascular calcification. Aim of this review is to present the pathophysiologic mechanisms underlying the activation and function of MGP and review the existing, accumulating data regarding the association between vitamin K, MGP and vascular calcification/CV disease in CKD patients.

show abstract

Matrix Gla protein T-138C polymorphism is associated with carotid intima media thickness and predicts mortality in patients with diabetic nephropathy

Cited by 38 publications

References 52 publications

Oxidative stress in hemodialysis: Causative mechanisms, clinical implications, and possible therapeutic interventions

Oxidative stress in hemodialysis: Causative mechanisms, clinical implications, and possible therapeutic interventions

Association of genetic polymorphisms in the Matrix Gla Protein (MGP) gene with coronary artery disease and serum mgp levels

Vascular Calcification in Chronic Kidney Disease: The Role of Vitamin K- Dependent Matrix Gla Protein

Contact Info

Product

Resources

About