Angiotensin-converting Enzyme Gene Polymorphism and Risk of Glucose Intolerance in Korean Men

ABSTRACT

Background: Prenatal exposure to Dutch famine was associated with glucose intolerance in adults. There is a line of evidence implicating the involvement of renin-angiotensin system in fetal development, but it is not known whether a genetic variant of reninangiotensin system may modify the long-term outcome in offspring born to mothers exposed to famine. Method: To examine whether an Insertion/Deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene is associated with glucose intolerance in subjects born during the famine in the Pacific War, 8,657 healthy men were studied. ACE genotypes were determined using polymerase chain reaction. Subjects with fasting glucose more than 6.1 mmol/l or those diagnosed as diabetes mellitus or current user of oral hypoglycemic agents or insulin were considered as glucose intolerance. Result: Among overall subjects, logistic regression analysis did not show a significant risk of ACE DD genotype for glucose intolerance (men OR 1.03; 95% CI, 0.88-1.21), but showed 42% increased risk in men (adjusted OR 1.42; 95% CI, 1.04-1.93, p=0.019), born during the war period, between 1941 and 1944. Conclusion: A genetic variant of renin-angiotensin system may modify the glucose intolerance as the long-term outcome in offspring born during the war-induced famine. Finding provides an evidence for the interaction of fetal ACE genotype and intrauterine environmental factor in predisposition to type 2 diabetes mellitus.