Genetic determinants and early carotid atherosclerosis: is there a role for the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP-1) K121Q polymorphism? Preliminary results in non diabetic individuals

Abstract

Carotid intima-media thickness (CIMT) is an intermediate phenotype for early atherosclerosis and a strong predictor of myocardial infarction and ischemic stroke [1]. Several studies have described the effects of candidate genes on CIMT, being unclear, however, the relative contribution of genetic variation to the development of the early stages of atherosclerosis [2]. The ectoenzyme pyrophosphatase phosphodiesterase 1 (ENPP-1) inhibits insulin receptor signaling [3]. A non synonymous polymorphism (K121Q, rs1044498) of the ENPP-1 gene is responsible for a gain of function of the protein [3], resulting in an increased ability to inhibit insulin receptor signaling. This variant has been associated with insulin resistance and type 2 diabetes in most studies [4, 5]. In agreement with the link between insulin resistance and cardiovascular disease (CVD), the Q121 variant has been shown to modulate susceptibility to premature myocardial infarction [6] and ischemic stroke [7] and to increase pulse pressure, a marker of arterial stiffness [8]. Some of these associations have been shown to be stronger in obese subjects, suggesting a gene-byobesity interaction in facilitating insulin resistance and atherogenic process [4, 9]. Up to date no results on ENPP-1 function on CIMT are available. Thus, we tested whether the ENPP-1 Q121 variant exerts an effect on CIMT measured at the common carotid artery (CCA) and at bulb and interacts with overweight–obesity in modulating CIMT.