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Angiotensin converting enzyme insertion/deletion polymorphism is associated with increased adiposity and blood pressure in obese children and adolescents
Authors:Vinícius AF Lemes  Ana Luísa Neves  Isabel C Guazzelli  Eliana Frazzatto  Christiane Nicolau  Maria Lúcia Corrêa-Giannella  Gilberto Velho  Sandra MF Villares
Institution:1. Laboratório de Endocrinologia Celular e Molecular (LIM-25), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil;2. INSERM, Research Unit 695, Paris, France;3. University of Porto (U.Porto), Faculty of Medicine, Porto, Portugal
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 7–16 years, 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  angiotensin converting enzyme  AUCglucose  area under the glucose curve during the OGTT (0&ndash  120   min)  BMI  body mass index  DBP  diastolic blood pressure  GWAS  genome-wide association study  I/D  insertion/deletion  ISIcomp  insulin sensitivity index  PH/AH  prehypertension/arterial hypertension combined trait  OGTT  oral glucose tolerance test  RAS  Renin&ndash  angiotensin system  SBP  systolic blood pressure
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