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

Francesco Perticone, Raffaele Maio, Rosa Di Paola, Angela Sciacqua, Antonella Marucci, Salvatore De Cosmo, Maria Perticone, Giorgio Sesti, Vincenzo Trischitta

Research output: Contribution to journalArticle

Abstract

Background and aim: Insulin 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 results: In 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. Conclusions: In 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.

Original languageEnglish
Pages (from-to)181-187
Number of pages7
JournalNutrition, Metabolism and Cardiovascular Diseases
Volume17
Issue number3
DOIs
Publication statusPublished - Mar 2007

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Keywords

  • Arterial hypertension
  • Cardiovascular disease
  • Gene polymorphism
  • Insulin resistance

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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