Matrix metalloproteinase-2 (MMP-2) gene polymorphism and cardiovascular comorbidity in type 2 diabetes patients

Kube

et al. 2018

Nephron

Aim: Aim of this study was to investigate the association of genetic variants of functional polymorphisms of matrix metalloproteinase and Cubilin (CUBN) with diabetic nephropathy (DN), end-stage renal disease (ESRD), and risk of cardiovascular disease (CVD) in Caucasian type 2 diabetes (T2D) patients. Methods: 472 T2D-patients were genotyped for 3 single-nucleotide polymorphisms (SNPs; MMP-2 [rs2285053], MMP-9 [rs17576] and CUBN [rs1801239]). Genotyping was carried out by allelic discrimination using TaqMan SNP-genotyping-assay. Results: MMP-9 (Gln279Arg) AA-genotype (OR 0.17 [0.04–0.62, p = 0.008]) and the time elapsed since diagnosis of T2D without onset of proteinuria (OR 0.87 [0.79–0.97, p = 0.008]) were found to be independently associated with reduced risk of susceptibility to DN. On the contrary higher stages of chronic kidney disease (OR 1.93 [1.15–3.23], p = 0.012) and the presence of MMP-9 GG-genotype were independently associated with DN (OR 6.07 [1.60–22.99], p = 0.008). The CUBN CC or C-risk-allele of rs1801239 was associated with ESRD (OR 2.04 [1.07–3.87], p = 0.03) and peripheral artery disease (OR 2.08 [1.12–3.88], p = 0.021). We could not find an association with MMP-2, MMP-9, or CUBN with CVD in a composite clinical endpoint model. Conclusions: This study highlights that MMP-9 or CUBN-SNPs may exert effects on risk of susceptibility to DN or ESRD. We provide novel evidence on genetic susceptibility for macroangiopathy in patients with a missense variant of CUBN (Ile2984Val) in patients with T2D.

Section: Interpretation Of Findings In Relationship Withcontrasting

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Cubilin Single Nucleotide Polymorphism Variants are Associated with Macroangiopathy While a Matrix Metalloproteinase-9 Single Nucleotide Polymorphism Flip-Flop may Indicate Susceptibility of Diabetic Nephropathy in Type-2 Diabetic Patients

Kube

et al. 2018

Nephron

“…In the SUMMIT cohort ( n = 985 subjects with T2DM and 515 controls), plasma levels of MMP-7 and MMP-12 were increased in patients with T2DM and were higher in patients with T2DM and CVD than in those without CVD [ 75 ]. In a study in 1090 patients with T2DM, the T allele of MMP-2 C (−1306)T polymorphism was associated with a lower risk of CVD and lower susceptibility to stroke [ 76 ].…”

Section: Matrix Metalloproteinasesmentioning

confidence: 99%

Novel Cardiovascular Risk Factors in Patients with Diabetic Kidney Disease

Kourtidou

Stangou

Marinaki

et al. 2021

IJMS

Patients with diabetic kidney disease (DKD) are at very high risk for cardiovascular events. Only part of this increased risk can be attributed to the presence of diabetes mellitus (DM) and to other DM-related comorbidities, including hypertension and obesity. The identification of novel risk factors that underpin the association between DKD and cardiovascular disease (CVD) is essential for risk stratification, for individualization of treatment and for identification of novel treatment targets.In the present review, we summarize the current knowledge regarding the role of emerging cardiovascular risk markers in patients with DKD. Among these biomarkers, fibroblast growth factor-23 and copeptin were studied more extensively and consistently predicted cardiovascular events in this population. Therefore, it might be useful to incorporate them in risk stratification strategies in patients with DKD to identify those who would possibly benefit from more aggressive management of cardiovascular risk factors.

“…Several reports have confirmed the inflammatory role of TNF-alpha, IL-6, and IL-10 [23]. Few studies have observed the associations between nephropathy in type 2 DM and chemokine gene polymorphisms [24] [25]. Previous investigators, stated that the major RANTES receptor (CCR5 promoter 59029A genotype) and the RANTES promoter (28G genotype) linked to diabetic nephropathy [24].…”

Section: Resultsmentioning

confidence: 95%

RANTES as a novel biomarker for atherogenic dyslipidemia and metabolic disturbances in patients with Type 2 Diabetes

et al. 2021

RANTES (Regulated upon Activation, Normal T cell Expressed and presumably Secreted) is a chemokine engaged in the pathophysiology of diabetes type 2 (T2DM), related cardiovascular complications, dyslipidemia and hypertension that are major modifiable risk factors of T2DM. VEGF (Vascular endothelial growth factor) plays a role in diabetic vascular complications. Atherogenic dyslipidemia (AD) is a lipid aberration defined as the incidence of raised triglycerides (TG) and dimished high-density lipoprotein cholesterol (HDL-C) and associated with residual cardiovascular risk. However, the association between chemokine and type 2 diabetes (T2DM) and metabolic disturbances is still unclear, and few data are available. The aim of this study was to estimate serum RANTES, serum lipid composition, VEGF, and metabolic syndrome (MS) in patients with T2DM and elucidate their relationship in a sample of Egyptian premenopausal women. Serum level of RANTES, VEGF, lipids and body composition were assessed in 100 premenopausal women with T2DM (mean age 35 years old) and 100 healthy controls. Significant increase in serum RANTES level and VEGF was observed in T2DM compared to the control group. Positive correlations between elevated RANETS and increased values of VEGF, body mass index (BMI), waist circumference (WC), fat mass, LDL-C, TG, total cholesterol and presence of MS were observed in T2DM patients. Elevated RANTES concentration is associated with AD risk, abnormal metabolic components and VEGF levels. This study pinpoints the importance of RANTES as a novel biomarker for dyslipidemia and metabolic disturbance in T2DM patients.