Genetic Predisposition to Left Ventricular Hypertrophy and the Potential Involvement of Cystatin-C in Untreated Hypertension

Tousoulis, Dimitris; Androulakis, Emmanuel; Papageorgiou, Nikolaos S.; Miliou, Antigoni; Chatzistamatiou, E.; Oikonomou, Evangelos; Moustakas, G.; Kallikazaros, Ioannis; Stefanadis, Christodoulos

doi:10.1093/ajh/hps089

Cited by 8 publications

(8 citation statements)

References 27 publications

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“…It appeared that all genes, presented in Table 1, except CST3, were associated with asthma and/or hypertension, according to the OMIM [85] and MalaCards [86] databases. However, the associations of this gene with asthma and hypertension are discussed in the literature [87][88][89].…”

Section: Prioritization Of Candidate Genesmentioning

confidence: 99%

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

et al. 2018

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Background: Hypertension and bronchial asthma are a major issue for people's health. As of 2014, approximately one billion adults, or~22% of the world population, have had hypertension. As of 2011, 235-330 million people globally have been affected by asthma and approximately 250,000-345,000 people have died each year from the disease. The development of the effective treatment therapies against these diseases is complicated by their comorbidity features. This is often a major problem in diagnosis and their treatment. Hence, in this study the bioinformatical methodology for the analysis of the comorbidity of these two diseases have been developed. As such, the search for candidate genes related to the comorbid conditions of asthma and hypertension can help in elucidating the molecular mechanisms underlying the comorbid condition of these two diseases, and can also be useful for genotyping and identifying new drug targets. Results: Using ANDSystem, the reconstruction and analysis of gene networks associated with asthma and hypertension was carried out. The gene network of asthma included 755 genes/proteins and 62,603 interactions, while the gene network of hypertension -713 genes/proteins and 45,479 interactions. Two hundred and five genes/proteins and 9638 interactions were shared between asthma and hypertension. An approach for ranking genes implicated in the comorbid condition of two diseases was proposed. The approach is based on nine criteria for ranking genes by their importance, including standard methods of gene prioritization (Endeavor, ToppGene) as well as original criteria that take into account the characteristics of an associative gene network and the presence of known polymorphisms in the analysed genes. According to the proposed approach, the genes IL10, TLR4, and CAT had the highest priority in the development of comorbidity of these two diseases. Additionally, it was revealed that the list of top genes is enriched with apoptotic genes and genes involved in biological processes related to the functioning of central nervous system.

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Section: Prioritization Of Candidate Genesmentioning

confidence: 99%

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

et al. 2018

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“…We have previously demonstrated that cystatin C levels are associated with higher LVMI values in untreated hypertensive patients . In this context, we sought to investigate for the first time to our knowledge, the possible link between cystatin C and WCH.…”

Section: Discussionmentioning

confidence: 99%

“…41 We have previously demonstrated that cystatin C levels are associated with higher LVMI values in untreated hypertensive patients. 18 In this context, we sought to investigate for the first time to our knowledge, the possible link between cystatin C and WCH. Cystatin C is a protein that is freely filtrated through the glomerulous and is considered a more sensitive marker of kidney dysfunction than creatinine, especially at higher estimated glomerular filtration rate levels.…”

Section: The Impact Of Wch On Arterial Stiffnessmentioning

confidence: 99%

“…[15][16][17] We have previously demonstrated that cystatin C levels correlate with higher LVMI values in untreated hypertensive individuals. 18 Nonetheless, its role in WCH has not been fully elucidated.…”

mentioning

confidence: 99%

“…Novel biomarkers such as cystatin C have only lately been acknowledged with regards to their correlation with CV risk . We have previously demonstrated that cystatin C levels correlate with higher LVMI values in untreated hypertensive individuals . Nonetheless, its role in WCH has not been fully elucidated.…”

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confidence: 99%

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Subclinical Organ Damage in White‐Coat Hypertension: The Possible Role of Cystatin C

Androulakis

Papageorgiou

Lioudaki

et al. 2016

J of Clinical Hypertension

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The authors investigated the relationship of white-coat hypertension (WCH) with subclinical organ damage and potential relevant mechanisms. A total of 386 untreated patients were enrolled and divided into 204 patients with WCH and 183 with normotension. Flow-mediated dilation (FMD), pulse wave velocity (PWV), intima-media thickness, left ventricular mass index (LVMI), and cystatin C levels were measured. All tests were two-sided, and a P value <.05 was considered statistically significant. The WCH group exhibited higher LVMI and PWV values, decreased E/A ratio and FMD values, and increased prevalence for left ventricular hypertrophy compared with controls (P<.001 for all). Cystatin C was significantly higher in the WCH group compared with controls (P=.035) and was positively associated with LVMI (P<.05 for both). The presence of WCH is associated with more pronounced subclinical organ damage compared with normotension. Cystatin C may play a significant role and therefore warrants further investigation.

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Can metabolically healthy obesity be explained by diet, genetics, and inflammation?

Navarro

Funtikova

Fitó

et al. 2015

Molecular Nutrition Food Res

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A substantial proportion of obese individuals do not present cardiometabolic complications such as diabetes, hypertension, or dyslipidemia. Some, but not all, prospective studies observe similar risk of cardiovascular events and all-cause mortality among individuals with this so-called "metabolically healthy obese" (MHO) phenotype, compared to the metabolically healthy normal weight or metabolically healthy non-obese phenotypes. Compared to the metabolically unhealthy obese (MUO) phenotype, MHO is often characterized by a more favorable inflammatory profile, less visceral fat, less infiltration of macrophages into adipose tissue, and smaller adipocyte cell size. Tipping the inflammation balance in adipose tissue might be particularly important for metabolic health in the obese. While the potential role of genetic predisposition or lifestyle factors such as diet in the MHO phenotype is yet to be clarified, it is well known that diet affects inflammation profile and contributes to the functionality of adipose tissue. This review will discuss genetic predisposition and the molecular mechanisms underlying the potential effect of food on the development of the metabolic phenotype characteristic of obesity.

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Genetic Predisposition to Left Ventricular Hypertrophy and the Potential Involvement of Cystatin-C in Untreated Hypertension

Abstract: We have shown that C-344T potentially predicts higher values of LVMI and concentric hypertrophy in untreated hypertension, independently of renal function and subclinical inflammation. Increased levels of cystatin-C were correlated with higher LVMI values.

Cited by 8 publications

References 27 publications

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

Subclinical Organ Damage in White‐Coat Hypertension: The Possible Role of Cystatin C

Can metabolically healthy obesity be explained by diet, genetics, and inflammation?

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