Abstract
Hypertension, diabetes and obesity are cardiovascular risk factors closely associated to the development of renal and cardiovascular target organ damage. VAV2 and VAV3, members of the VAV family proto-oncogenes, are guanosine nucleotide exchange factors for the Rho and Rac GTPase family, which is related with cardiovascular homeostasis. We have analyzed the relationship between the presence of VAV2 rs602990 and VAV3 rs7528153 polymorphisms with cardiovascular risk factors and target organ damage (heart, vessels and kidney) in 411 subjects. Our results show that being carrier of the T allele in VAV2 rs602990 polymorphism is associated with an increased risk of obesity, reduced levels of ankle-brachial index and diastolic blood pressure and reduced retinal artery caliber. In addition, being carrier of T allele is associated with increased risk of target organ damage in males. On the other hand, being carrier of the T allele in VAV3 rs7528153 polymorphism is associated with a decreased susceptibility of developing a pathologic state composed by the presence of hypertension, diabetes, obesity or cardiovascular damage, and with an increased risk of developing altered basal glycaemia. This is the first report showing an association between VAV2 and VAV3 polymorphisms with cardiovascular risk factors and target organ damage.
Highlights
Sauzeau et al.[20] analysed the effects of the absence of VAV2 in knock-out mice, which showed cardiovascular alterations such as cardiovascular remodeling, thickening of aorta media walls and left ventricular hypertrophy (LVH) with fibrosis
Several studies have observed that some single nucleotide polymorphisms (SNPs) in VAV genes are related to pathologies such as schizophrenia (VAV3 rs1410403)[23], hypothyroidism (VAV3 rs4915077)[24] and candidate genes for spontaneous glaucoma (VAV2 rs2156323 and VAV3 rs2801219)25- albeit later studies seem to rule out this involvement[26], there are not studies relating VAV polymorphisms with cardiovascular risk
A paraoxonase 1 polymorphism is related with low-density lipoprotein cholesterol levels and with the risk of premature myocardial infarction, whereas another polymorphism of the same gene is associated with a positive family history of coronary artery disease[29]
Summary
Sauzeau et al.[20] analysed the effects of the absence of VAV2 in knock-out mice, which showed cardiovascular alterations such as cardiovascular remodeling, thickening of aorta media walls and LVH with fibrosis These mice showed renal fibrosis, tachycardia and HT due to hyperstimulation of the renin/angiotensin/aldosterone axis and sympathetic nervous system[20]. They observed a similar phenotype in VAV3−/− mice (cardiovascular remodeling, HT, tachycardia, kidney and heart fibrosis)[21], suggesting that both VAV2 and VAV3 play a key role in cardiovascular homeostasis[20,21]. Our aim is to analyze the relationship between VAV2 (rs602990) and VAV3 (rs7528153) polymorphisms with cardiovascular risk factors and TOD (heart, vessels and kidney) in a Spanish population[8]
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