K121Q Polymorphism of the ENPP1 gene is related to acute coronary syndrome in Ukrainian patients with normal but not enhanced body mass index

Abstract

Ectonucleotide Pyrophosphatase Phosphodiesterase 1 (ENPP1) is a class II membrane glycoprotein with two unrelated properties: It can hydrolyze extracellular nucleotides and downregulate insulin receptor signaling. The present study was carried out to investigate whether common single-nucleotide polymorphism K121Q (rs1044498) of the ENPP1 gene is associated with Acute Coronary Syndrome (ACS) in the representatives of Ukrainian population and to assess if the risk depends on gender and Body Mass Index (BMI). A total 228 DNA samples (118 ACS patients and 110 control subjects) were genotyped for the polymorphism by PCR and restriction fragment length polymorphism method. No associations between the K121Q polymorphisms and ACS were found neither on the whole nor taking into account the gender. However, in the persons with BMI <25 kg/m2 but not with overweight, genotypes with the minor allele (KQ + QQ) were significantly associated with ACS (OR 3.939, 95% CI 1.148-13.524, P = 0.029). Genotypes with minor allele can be a possible genetic risk factor for ACS in persons with BMI <25 kg/m2. It is likely that these genotypes affect ACS not by the traditional risk factors (overweight/obesity, insulin resistance and type 2 diabetes) but by direct or undirect influence on pathologic processes in the wall of the coronary vessels (atherosclerosis and arterial calcification).