Gene expression in peripheral blood of patients with hypertension and patients with type 2 diabetes

Stoynev, Nikolay; Dimova, Ivanka; Rukova, Blaga; Hadjidekova, Savina; Nikolova, Dragomira; Toncheva, Draga; Tankova, Tsvetalina

doi:10.2459/jcm.0b013e32835dbcc8

Cited by 28 publications

(30 citation statements)

References 40 publications

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“…in peripheral blood, a material much more easily obtained in patients with hypertension, also found regulation of expression of genes involved in major histocompatibility complex class II receptor activity and immune response. Another study in peripheral blood by Stoynev et al 21 . compared gene expression profiles between patients with hypertension, those with type 2 diabetes, and controls and found PDGFRB , encoding platelet-derived growth factor beta, significantly regulated.…”

Section: Transcriptomicsmentioning

confidence: 99%

The Future of “Omics” in Hypertension

Currie

Delles

2017

Canadian Journal of Cardiology

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Despite decades of research and clinical practice, the pathogenesis of hypertension remains incompletely understood, and blood pressure is often suboptimally controlled. “Omics” technologies allow the description of a large number of molecular features and have the potential to identify new factors that contribute to blood pressure regulation and how they interact. In this review, we focus on the potential of genomics, transcriptomics, proteomics, and metabolomics and explore their roles in unraveling the pathophysiology and diagnosis of hypertension, the prediction of organ damage and treatment response, and monitoring treatment effect. Substantial progress has been made in the area of genomics, in which genome-wide association studies have identified > 50 blood pressure–related, single-nucleotide polymorphisms, and sequencing studies (especially in secondary forms of hypertension) have discovered novel regulatory pathways. In contrast, other omics technologies, despite their ability to provide detailed insights into the physiological state of an organism, have only more recently demonstrated their impact on hypertension research and clinical practice. The majority of current proteomic studies focus on organ damage resulting from hypertension and may have the potential to help us understand the link between blood pressure and organ failure but also serve as biomarkers for early detection of cerebrovascular or coronary disease. Examples include signatures for early detection of left ventricular dysfunction or albuminuria. Metabolomic studies have the potential to integrate environmental and intrinsic factors and are particularly suited to monitor the response to treatment. We discuss examples of omics studies in hypertension and explore the challenges related to these novel technologies.

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Section: Transcriptomicsmentioning

confidence: 99%

The Future of “Omics” in Hypertension

Currie

Delles

2017

Canadian Journal of Cardiology

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Section: Chan Et Al Pathways Of Cvd and T2d In Multiple Ethnicities 915mentioning

confidence: 99%

“…Soluble intercellular adhesion molecules and vascular cell adhesion molecules have been associated with the development of coronary heart disease in the Health Professional Follow-up Study. 40 Higher levels of intercellular adhesion molecule-1 were also consistently associated with increased T2D risk in the WHI-Observational Study.3 Therefore, these pathways appear to link to CVD and T2D via diverse mechanisms. The fact that these pathways were consistently identified across multiple ethnicities in our study highlights their central role in the joint mechanisms between CVD and T2D.…”

mentioning

confidence: 99%

Shared Molecular Pathways and Gene Networks for Cardiovascular Disease and Type 2 Diabetes Mellitus in Women Across Diverse Ethnicities

Chan

Huang

Meng

et al. 2014

Circ Cardiovasc Genet

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It has long been known that cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D) share many common risk factors and pathophysiological intermediaries including obesity, dyslipidemia, insulin resistance, and proinflammatory and prothrombotic states. [1][2][3] However, the key molecular drivers underlying these highly correlated phenotypes as well as the potential regulatory networks shared in the pathogenesis of CVD and T2D remain poorly understood. Clinical Perspective on p 919Of the ≈60 genetic loci identified for CVD and T2D in large-scale genome-wide association studies (GWAS), 5 only 2 significant loci (TCF7L2 and VEGFA) are shared between the 2 diseases. There are ≥3 fundamentally important questions that remain to be answered. First, are there additional genetic risks, either alone or concentrated in specific regulatory networks that may explain the pathophysiological connections between CVD and T2D? Second, are there any ethnicityspecific genetic mechanisms for these 2 common vascular diseases, given that there are drastic ethnicity-specific differences in their risk and linkage disequilibrium patterns. [6][7][8] Third, although common genetic loci have been detected across different populations (eg, the Chr9p21 locus for CVD and the TCF7L2 locus for T2D) supporting the presence of common pathological paths across ethnicity, to what degree molecular mechanisms are shared across ethnicities?To answer these 3 questions, we performed 2 GWAS for both CVD and T2D using an integrative pathway and network analysis in the national Women's Health Initiative SNP Health Association Resource (WHI-SHARe) and the Genomics and Background-Although cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D) share many common risk factors, potential molecular mechanisms that may also be shared for these 2 disorders remain unknown. Methods and Results-Using an integrative pathway and network analysis, we performed genome-wide association studies in 8155 blacks, 3494 Hispanic American, and 3697 Caucasian American women who participated in the national Women's Health Initiative single-nucleotide polymorphism (SNP) Health Association Resource and the Genomics and Randomized Trials Network. Eight top pathways and gene networks related to cardiomyopathy, calcium signaling, axon guidance, cell adhesion, and extracellular matrix seemed to be commonly shared between CVD and T2D across all 3 ethnic groups. We also identified ethnicity-specific pathways, such as cell cycle (specific for Hispanic American and Caucasian American) and tight junction (CVD and combined CVD and T2D in Hispanic American). In network analysis of gene-gene or protein-protein interactions, we identified key drivers that included COL1A1, COL3A1, and ELN in the shared pathways for both CVD and T2D. These key driver genes were cross-validated in multiple mouse models of diabetes mellitus and atherosclerosis. Conclusions-Our integrative analysis of American women of 3 ethnicities identified multiple shared biological pathways and key regulatory ge...

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“…The expression of these genes from healthy through the increasing stages may not therefore be linear as in the case of serum creatinine, and the correlations seen may not indicate a relationship between the parameters, but individually regulatory mechanisms. For example, FN1 expression in blood has been associated with hypertension where increased expression was seen in hypertensive patients, being involved in protective mechanisms that limit organ damage [52]. The increased expression in early stage CKDu could be an initial protective effect which again diminishes with disease progression.…”

Section: Discussionmentioning

confidence: 99%

Potential diagnostic biomarkers for chronic kidney disease of unknown etiology (CKDu) in Sri Lanka: a pilot study

Saravanabavan

Magana-Arachchi

Gunerathne³

et al. 2017

BMC Nephrol

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BackgroundIn Sri Lanka, there exists chronic kidney disease of both known (CKD) and unknown etiologies (CKDu). Identification of novel biomarkers that are customized to the specific causative factors would lead to early diagnosis and clearer prognosis of the diseases. This study aimed to find genetic biomarkers in blood to distinguish and identify CKDu from CKD as well as healthy populations from CKDu endemic and non-endemic areas of Sri Lanka.MethodsThe expression patterns of a selected panel of 12 potential genetic biomarkers were analyzed in blood using RT-qPCR. Fold changes of gene expressions in early and late stages of CKD and CKDu patients, and an apparently healthy population of a CKDu endemic area, Girandurukotte (GH) were calculated relative to apparently healthy volunteers from a CKDu non-endemic area, Kandy (KH) of Sri Lanka, using the comparative CT method.ResultsSignificant differences were observed between KH and early stage CKDu for both the insulin-like growth factor binding protein 1 (IGFBP1; p = 0.012) and kidney injury molecule-1 (KIM1; p = 0.003) genes, and KH and late stage CKD and CKDu for the glutathione-S-transferase mu 1 (GSTM1; p < 0.05) gene. IGFBP1 and KIM1 genes showed significant difference between the early and late stage CKDu (p < 0.01). The glutamate cysteine ligase catalytic subunit (GCLC) gene had significantly different expression between KH and all the other study groups (p < 0.01). The GH group was significantly different from the KH group for the oxidative stress related genes, G6PD, GCLC and GSTM1 (p < 0.01), and also the KIM1 gene (p = 0.003). IGFBP1, insulin-like growth factor binding protein 3 (IGFBP3), fibronectin 1 (FN1) and KIM1 showed significant correlations with serum creatinine, and IGFBP1, KIM1 and kallikrein 1 (KLK1) with eGFR (p < 0.05).ConclusionA panel consisting of IGFBP1, KIM1, GCLC and GSTM1 genes could be used in combination for early screening of CKDu, whereas these genes in addition with FN1, IGFBP3 and KLK1 could be used to monitor progression of CKDu. The regulation of these genes has to be studied on larger populations to validate their efficiency for further clinical use.

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Gene expression in peripheral blood of patients with hypertension and patients with type 2 diabetes

Cited by 28 publications

References 40 publications

The Future of “Omics” in Hypertension

The Future of “Omics” in Hypertension

Shared Molecular Pathways and Gene Networks for Cardiovascular Disease and Type 2 Diabetes Mellitus in Women Across Diverse Ethnicities

Potential diagnostic biomarkers for chronic kidney disease of unknown etiology (CKDu) in Sri Lanka: a pilot study

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