Angiotensin converting enzyme insertion/deletion polymorphism is associated with increased adiposity and blood pressure in obese children and adolescents

Gene. 2013 Dec 15;532(2):197-202. doi: 10.1016/j.gene.2013.09.065. Epub 2013 Sep 26.

Abstract

Background: The insertion/deletion polymorphism in the gene encoding the angiotensin-converting enzyme (ACE I/D) was associated with arterial hypertension and obesity in adults, but the data in children are scarce and yielded contrasting results. We assessed the impact of the ACE I/D on blood pressure and obesity related traits in a Brazilian cohort of obese children and adolescents.

Methods and results: ACE I/D was genotyped in 320 obese children and adolescents (64% of girls) aged 7-16years, referred for a weight-loss program. We observed an association of the D-allele with blood pressure and with pre-hypertension/hypertension in boys (odds ratio 2.44, 95% C.I. 1.34-4.68, p=0.005 for a codominant model). The D-allele, insulin resistance and body fat mass had independent and additive effects and explained 14% of the variance of pre-hypertension/hypertension. The BMI, waist circumference, and body fat mass were significantly higher in DD/ID boys than in II boys (p<0.005). Allelic associations with obesity related traits were independent of the association with blood pressure. No genotype associations were observed in girls.

Conclusions: The D-allele of the ACE I/D polymorphism was associated with arterial hypertension and with obesity related traits in boys, but not in girls, in a cohort of obese children and adolescents. These associations were independent of each other, as well as of the effects of other confounding traits such as insulin secretion, insulin sensitivity and glucose tolerance. Our results are in agreement with experimental evidences suggesting that the renin-angiotensin system plays a role in the regulation of visceral adipose tissue accumulation.

Keywords: ACE; ACE I/D polymorphism; AUC(glucose); Arterial hypertension; BMI; Children; DBP; GWAS; I/D; ISI(comp); OGTT; Obesity; PH/AH; RAS; Renin–angiotensin system; SBP; angiotensin converting enzyme; area under the glucose curve during the OGTT (0–120min); body mass index; diastolic blood pressure; genome-wide association study; insertion/deletion; insulin sensitivity index; oral glucose tolerance test; prehypertension/arterial hypertension combined trait; systolic blood pressure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / genetics*
  • Adolescent
  • Arterial Pressure / genetics
  • Child
  • Cohort Studies
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Hypertension / enzymology
  • Hypertension / genetics*
  • INDEL Mutation*
  • Intra-Abdominal Fat / enzymology
  • Intra-Abdominal Fat / pathology
  • Male
  • Obesity / enzymology
  • Obesity / genetics*
  • Obesity / physiopathology
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic

Substances

  • ACE protein, human
  • Peptidyl-Dipeptidase A