Association between angiotensin-converting enzyme gene polymorphisms and QT duration in a multiethnic population in Hawaii

Objectives: Recent studies have suggested that heart-rate corrected QT interval (QTc) in normal populations may be influenced by genetic factors. We report findings of a study of the relationship between QTc, increased QTc (> 440 ms) and angiotensin-converting enzyme (ACE) genotype in a multiethnic, population-based study completed in rural Hawaii. Methods: Blood samples were obtained while fasting and after an oral glucose challenge from 1452 individuals between 1997 and 2000. The clinical examination included an electrocardiogram. Medical histories, behavioral and socio-demographic information were obtained during the interview. Ethnicity was estimated by self-report. The insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene was determined by polymerase chain reaction (PCR) from a random sample of 588 participants. Multiple linear and logistic regression was used to test for associations between QTc and ACE gene polymorphisms. Results: The overall crude prevalence of increased QTc was 21.2%. The prevalence of increased QTc was lowest among those with ACE DD genotype, and highest among those with ACE insertion/insertion (II) genotype. The adjusted odds ratio for increased QTc was 2.29 (95% CI 1.02-5.12) and 3.61 (95% CI 1.60-8.13) for ID and II genotypes, respectively, compared to the DD genotype. The test for trend was highly significant (p < 0.001). Conclusions: The ACE insertion allele was associated with increased prevalence of prolonged QTc independent of ethnicity, age, gender, and BMI. These findings may implicate the ACE gene as an important genetic risk factor for cardiovascular disease morbidity and mortality.