Neuropeptide Y T1128C polymorphism

Abstract

Neuropeptide Y (NPY) is generally considered to play an important role in central and peripheral neural regulation, cardiovascular control and blood pressure homeostasis [1]. NPY is a 36-amino acid peptide that was initially isolated from porcine brain by Tatemoto et al. [2]. It belongs to a family of polypeptide hormones, including pancreatic polypeptides and peptide YY [2]. Because NPY is most abundant in the mammalian brain and peripheral sympathetic nerve terminals where it is colocalized with noradrenaline [3], it was classically viewed as a neuropeptide or neurotransmitter. However, following its discovery, NPY has been shown to exert diverse biological actions on central and peripheral neural regulation, cholesterol metabolism, appetite and behaviour, and cardiovascular and blood pressure homeostasis. The neural and cardiovascular effects of NPY and its possible role in hypertension have been the subject of several recent reviews [1,[4][5][6][7]. In vitro, NPY exerts both postjunctional inotropic and chronotropic effects on cardiac tissue involving L-type Ca 2+ currents and pacemaker currents by acting on specific pre-and postsynaptic receptors [1,7]. NPY also induces cardiac hypertrophy by stimulating cardiac myocyte growth, and angiogenic effects by promoting vascular sprouting and capillary tube formation by endothelial cells [7,8]. In vivo, the cardiovascular actions of NPY are more complex and appear to depend on the species and the site or mode of administration; these effects are often difficult to reconcile from one study to another [1]. There have been reports of NPY involving both an increase and decrease in cardiac output, both vasoconstriction and vasodilatation, and both an increase and decrease in blood pressure induced by NPY have been reported [1]. Thus, the precise role(s) and mechanism(s) of NPY with respect to cardiovascular regulation and blood pressure control in humans remain largely unknown. Against the vast literature on possible roles of NPY published to date, in the current issue of the journal, Wallerstedt et al. [9] report a significant association between a NPY gene T1128C polymorphism [Leu(7)-to-Pro(7)] and myocardial infarction and stroke in a Swedish hypertensive population. This study approaches NPY research from a clinical perspective, and its findings may contribute new information to our understanding of the potential role of NPY in human cardiovascular physiology and diseases.Association analysis of gene polymorphisms and human diseases is a powerful tool for defining the effects of genetic factors on the development and progression of disease. Information derived from these studies may be useful in devising new strategies to prevent and treat human disease. Because of its potential effects on cardiovascular and blood pressure regulation [1,4,5,7], the association between NPY gene polymorphism and cardiovascular diseases has been the focus of several studies in animals and humans. Although the study by Wallerstedt et al. [9] was not the first attempt to identify an ass...

Lack of an Association between a Functional Polymorphism in the Neuropeptide Y Gene Promoter and the Presence of Coronary Artery Disease in an Iranian Population

“…NPY plays an important role in cardiovascular pathophysiology, being involved in controlling vascular tone, inhibiting norepinephrine release and potentiating responses to norepinephrine [15,16]. NPY is therefore involved in endothelial and heart functions, but there are few studies evaluating the variations in the encoding gene and their contribution to cardiovascular disease risk [17]. …”