Influence of fat intake and BMI on the association of rs1799983 NOS3 polymorphism with blood pressure levels in an Iberian population

Abstract

Introduction Hypertension contributes to the burden of heart disease, stroke, kidney failure and premature mortality [1]. In fact, hypertension complications account for 9.4 million deaths worldwide every year [2]. Key risk factors include age, race, endocrine and metabolic disorders, lifestyle behaviors and genetics, among others [1]. In this context, familial and twin studies have estimated the heritable component of Blood Pressure (BP) to be about 30%-60% [3]. Moreover, Genome Wide Association Studies (GWAS) have identified a large number of polymorphisms associated with BP or hypertension, which are located in or near genes involved in the renin-angiotensin-aldosterone system, related to enzymes and receptors of the mineral-and glucocorticoid pathways and associated with proteins implicated in the structure and/or regulation of vascular tone [4].Among them, the Nitric Oxide Synthase (NOS3) gene is regarded as one of the putative candidate gene for BP regulation and hypertension, since it is involved in the production of Nitric Oxide (NO) which has vasodilator effects (i.e. inhibiting vascular smooth muscle contraction) [5]. Indeed, it has been observed in an animal model that the disruption of NOS3 gene led to hypertension, while in humans the inhibition of NOS3 elevated BP [5, 6]. Between NOS3 genetic variants, the rs1799983 is the most recognized polymorphism related not only to BP and hypertension, but also to coronary artery and vascular diseases, myocardial infarction, metabolic syndrome and type 2 diabetes [7]. Unfortunately, the results of studies seeking associations of rs1799983 and BP or hypertension have not always been consistent in different populations, which might be due to gene-environmental risk factors interactions [8]. However, to our knowledge, there are few reports on the modulation of environmental factors such as excess body weight or diet, two risk factors widely associated with increased BP levels and hypertension, on the association between rs1799983 and BP or hypertension [9, 10]. Therefore, the aims of the present research were to examine the potential association between the rs1799983 NOS3 genetic variant and BP levels and hypertension, and to investigate the possible influence of non-genetic risk factors on that association.