Role of PC-1 and ACE genes on insulin resistance and cardiac mass in never-treated hypertensive patients. Suggestive evidence for a digenic additive modulation

Background and aimInsulin resistance and increased left ventricular mass (LVM) characterize patients with essential hypertension. Some genetic polymorphisms play a role in the modulation of both insulin resistance and LVM. The aim of this work was to investigate whether the PC-1 and ACE genes exert a polygenic control of insulin resistance and LVM in hypertensive patients.Methods and resultsIn 158 never-treated hypertensive patients, we evaluated insulin resistance by HOMA index [insulin (μU/mL) × glucose (mmol/L)]/22.5 and LVM by echocardiograms. Genetic polymorphisms were obtained by polymerase chain reaction. PC-1 X121Q genotype carriers (K121Q + Q121Q, n = 46) had higher HOMA (3.14 ± 1.28 vs. 2.49 ± 1.25; p = 0.002) and LVM (137 ± 34 vs. 127 ± 24 g/m2; p = 0.02) than K121K patients (n = 112). Similarly, ACE DD carriers (n = 56) showed higher HOMA (3.94 ± 1.13 vs. 1.98 ± 0.72; p < 0.00001) and LVM (142 ± 26 vs. 123 ± 25 g/m2; p = 0.00004) than XI (ID + II, n = 102) patients. When considering both PC-1 and ACE polymorphisms, HOMA (p < 0.00001) and LVM (p = 0.00003) progressively increased from K121K/XI to X121Q/XI, K121K/DD and X121Q/DD patients. The association of both gene polymorphisms with LVM was no longer significant after adjusting for HOMA values. As compared to K121K/XI patients (i.e. no at risk alleles), X121Q/DD patients had a significantly increased risk (OR: 4.4, 95% C.I. 1.4–14.0, p = 0.011) to have left ventricular hypertrophy.ConclusionsIn hypertensive patients PC-1 K121Q and ACE I/D polymorphisms have an additive deleterious effect on insulin resistance and, consequently, on LVM, thus increasing the global cardiovascular risk. Identification of carriers of the at-risk genotypes may help set up prevention strategies to be specifically targeted at these patients.