G-6A Polymorphism of the Angiotensinogen Gene and Its Association With Left Ventricular Mass in Asymptomatic Young Adults from a Biethnic Community: The Bogalusa Heart Study

Abstract

Angiotensinogen (AGT), the precursor of angiotensin II and a rate limiting factor in the renin-angiotensin system, is implicated in left ventricular hypertrophy, as angiotensin II is a potent stimulator of cardiac growth. A genetic variant (G-6A) in the proximal promoter region of the AGT gene may be particularly important for changes in left ventricular mass (LVM). However, previous findings associating this variant with LVM among relatively older adults with cardiovascular morbidity are inconsistent and contradictory. This study examined the effect of G-6A polymorphism on LVM in a biethnic (African American and white), community-based sample of 362 asymptomatic younger adults (mean age 32.5 years, 71% white, 39% male). Two-dimensional M-mode echocardiography was used to assess LVM, and the indexation of LVM for height(2.7) (LVMI) was used to adjust for body size. The frequency of the variant A(-6) allele was higher in subjects of African American than in white ethnicity (0.819 v 0.439, P < .0001), with carriers (GA+AA) representing 97.0% of African American as compared to 66.6% of white subjects. After adjusting for age, ethnicity (for total sample), gender, body mass index, systolic BP, and homeostasis model assessment index of insulin resistance, mean levels for both LVM and LVMI showed a significant decreasing trend with increasing gene dosage of the A(-6) allele in white subjects, African American subjects, and the total sample. These results indicate that the A(-6) allele frequency differs markedly between African Americans and white individuals, and that the variant allele modulates LVM and LVMI in a beneficial manner in asymptomatic young adults of white and African American ethnicities.