Genetic and environmental determinants of hepatocyte growth factor levels and their association with obesity and blood pressure

Vistoropsky, Yulia; Trofimov, Svetlana; Malkin, Ida; Kobyliansky, Eugene; Livshits, Gregory

doi:10.1080/03014460701822003

Cited by 21 publications

(19 citation statements)

References 35 publications

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“…BMI, waist circumference and WHR) that showed pleiotropic effects in other populations. The accepted measure of obesity in populations and in clinical practice (BMI) has shown to be genetically correlated with BP in several studies [8][9][10][11] as well as WHR [11,12] and waist circumference [11]. Waist circumference has been found to be a good indicator of abdominal fat and some authors have suggested that this trait could be even a more appropriate obesity indicator and a better predictor of CVDs than BMI in adults [47], adolescents [48] and in children [49].…”

Section: Discussionmentioning

confidence: 99%

“…The most commonly reported adiposity measures in relation to BP phenotypes include weight, waist circumference, skinfolds thickness and indices such as BMI and waist-to-hip ratio (WHR) [7][8][9][10][11][12][13][14]. Factors extracted from a factor analysis could represent features that contain a higher degree of genetic variance than the original variables separately [15].…”

Section: Introductionmentioning

confidence: 99%

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A statistical investigation into the sharing of common genetic factors between blood pressure and obesity phenotypes in nuclear families from the Greater Bilbao (Spain)

Jelenkovic

Poveda

Rebato

2010

Journal of Hypertension

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A statistical investigation into the sharing of common genetic factors between blood pressure and obesity phenotypes in nuclear families from the Greater Bilbao (Spain)

Jelenkovic

Poveda

Rebato

2010

Journal of Hypertension

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“…Previous family-based analyses reported heritability estimates of 38% 6 and 48%, 20 respectively, for HGF levels. In small clinical samples, few genetic variants in the HGF gene have been tested for association with HGF levels revealing inconsistent results.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study for Endothelial Growth Factors

Lieb

Chen

Larson

et al. 2015

Circ Cardiovasc Genet

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Background Endothelial growth factors including angiopoietin-2 (Ang-2), its soluble receptor Tie-2 (sTie-2) and hepatocyte growth factor (HGF) play important roles in angiogenesis, vascular remodeling, local tumor growth and metastatic potential of various cancers. Circulating levels of these biomarkers have a heritable component (between 13% and 56%), but the underlying genetic variation influencing these biomarker levels is largely unknown. Methods and Results We performed a genome-wide association study for circulating Ang-2, sTie-2, and HGF in 3571 Framingham Heart Study (FHS) participants and assessed replication of the top hits for Ang-2 and sTie-2 in 3184 participants of the Study of Health in Pomerania (SHIP). In multivariable-adjusted models, sTie-2 and HGF concentrations were associated with single nucleotide polymorphisms (SNPs) in the genes encoding the respective biomarkers (top p=2.40×10−65 [rs2273720] and 3.64×10−19 [rs5745687], respectively). Likewise, rs2442517 in the MCPH1 gene (in which the Ang-2 gene is embedded) was associated with Ang-2 levels (p=5.05×10−8 in FHS and 8.39×10−5 in SHIP). Furthermore, SNPs in the AB0 gene were associated with sTie-2 (top SNP rs8176693 with p=1.84×10−33 in FHS; p=2.53×10−30 in SHIP) and Ang-2 (rs8176746 with p=2.07×10−8 in FHS; p=0.001 in SHIP) levels on a genome-wide significant level. The top genetic loci explained between 1.7% (Ang-2) and 11.2% (sTie-2) of the inter-individual variation in biomarker levels. Conclusions Genetic variation contributes to the inter-individual variation in growth factor levels and explains a modest proportion of circulating HGF, Ang-2, and Tie-2. This may potentially contribute to the familial susceptibility to cancer, a premise that warrants further studies.

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“…In obese individuals, circulating HGF levels were increased by more than 3-fold, when compared to lean individuals (27). HGF levels have also been correlated with anthropometric measures of obesity such as waist circumference, body mass index and body fat mass (24, 30). Furthermore, an association between weight loss induced by bariatric surgery and reduced HGF levels was previously observed, in obese patients (22, 28).…”

Section: Role Of Adipose Tissue Derived Hgfmentioning

confidence: 99%

The Role of Hepatocyte Growth Factor (HGF) in Insulin Resistance and Diabetes

et al. 2018

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In obesity, insulin resistance (IR) and diabetes, there are proteins and hormones that may lead to the discovery of promising biomarkers and treatments for these metabolic disorders. For example, these molecules may impair the insulin signaling pathway or provide protection against IR. Thus, identifying proteins that are upregulated in IR states is relevant to the diagnosis and treatment of the associated disorders. It is becoming clear that hepatocyte growth factor (HGF) is an important component of the pathophysiology of IR, with increased levels in most common IR conditions, including obesity. HGF has a role in the metabolic flux of glucose in different insulin sensitive cell types; plays a key role in β-cell homeostasis; and is capable of modulating the inflammatory response. In this review, we discuss how, and to what extent HGF contributes to IR and diabetes pathophysiology, as well as its role in cancer which is more prevalent in obesity and diabetes. Based on the current literature and knowledge, it is clear that HGF plays a central role in these metabolic disorders. Thus, HGF levels could be employed as a biomarker for disease status/progression, and HGF/c-Met signaling pathway modulators could effectively regulate IR and treat diabetes.

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Genetic and environmental determinants of hepatocyte growth factor levels and their association with obesity and blood pressure

Cited by 21 publications

References 35 publications

A statistical investigation into the sharing of common genetic factors between blood pressure and obesity phenotypes in nuclear families from the Greater Bilbao (Spain)

A statistical investigation into the sharing of common genetic factors between blood pressure and obesity phenotypes in nuclear families from the Greater Bilbao (Spain)

Genome-Wide Association Study for Endothelial Growth Factors

The Role of Hepatocyte Growth Factor (HGF) in Insulin Resistance and Diabetes

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