Age is a strong risk factor for hypertension in relation to vascular aging. Additional etiological factors include: lifestyle, genetic factors, and their interactions. The aim of this study is to examine whether an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene is associated with essential hypertension in Korean born during the Pacific War. A total of 13,914 healthy subjects (8261 men, 5653 women) aged 20-79 years were examined. Subjects with abnormal renal, thyroid dysfunction, or electrolyte levels were excluded. Logistic regression analysis showed increased risk (OR = 1. 15; 95% Cl, 1.01-1.31) in men, but not in women (OR, 1.06; 95% Cl, 0.89-1.26). However, after adjustment for age, obesity, cholesterol, alcohol consumption, and diabetes mellitus, increased risk in men was not significant (OR, 1. 13; 95% Cl, 0.98-1.42). Analyzed according to birth-year, DD genotype showed increased risk for hypertension in only a subgroup of men (adjusted OR, 1.56; 95% Cl, 1.16-2.09; p = 0.001), born during the Pacific War (1941-1945 year). Findings suggest that the ACE DD genotype plays a role in the pathogenesis of essential hypertension, in conjunction with adverse environmental conditions in early life, with sex-related difference. (c) 2005 Elsevier Ireland Ltd. All rights reserved.