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J Hypertens. 2018 Nov;36(11):2168-2176. doi: 10.1097/HJH.0000000000001816.

Childhood adiposity, adult adiposity, and the ACE gene insertion/deletion polymorphism: evidence of gene-environment interaction effects on adult blood pressure and hypertension status in adulthood.

Author information

Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne.
Department of Paediatrics, University of Melbourne.
Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, Victoria.
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku and Turku University Hospital, Turku, Finland.
College of Public Health, University of Iowa, Iowa City, Iowa, USA.
Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine University of Tampere, Tampere.
Department of Medicine, University of Turku.
Division of Medicine, Turku University Hospital, Turku, Finland.
The George Institute for Global Health, Oxford University, Oxford, UK.



Genetic variants may modify the associations of adiposity measures with blood pressure (BP) and hypertension. The insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene is an attractive candidate.


To examine interaction effects between I/D polymorphism and adiposity measures (BMI, waist circumference, waist-to-hip ratio, and skinfold thickness) during childhood and adulthood in relation to adult BP and hypertension.


Data were available for 4835 participants from three prospective cohort studies. Multivariable linear regression models for adult SBP and DBP, and multivariable logistic regression models for hypertension were fit that included interaction effects between child or adult adiposity and I/D polymorphism.


Evidence for interaction effects on BP/hypertension were found across the three studies. Compared with childhood measures, the effect modification appeared to be more consistent when using adult adiposity. In particular, the adverse effects of greater adult waist circumference on increasing adult SBP and DBP appeared to be larger among carriers of ACE DD (or GG) [adjusted linear regression coefficients 0.26, 95% CI (0.21-0.31) and 0.28 (0.24-0.32) for SBP and DBP, respectively] and ID (or AG) genotypes [0.25 (0.21-0.29) and 0.25 (0.21-0.28), respectively], whereas those with II (or AA) genotypes had smaller effects [0.15 (0.09-0.21) and 0.19 (0.13-0.23)].


ACE genetic variation may modify the effect of adult adiposity on increasing BP and risk of hypertension in adulthood. Individuals with ACE DD (or GG) and/or ID (or AG) genotypes, compared with those with II (or AA) genotype, appear more vulnerable to the impact of excess adiposity.

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