Effects of Angiotensinogen and Angiotensin II Type I Receptor Genes on Blood Pressure and Left Ventricular Mass Trajectories in Multiethnic Youth

The objective of this study was to evaluate the impact of variations of the angiotensinogen (AGT) and angiotensin II type I receptor (AGTR1) genes on progression of blood pressure (BP) and left ventricular mass (LVM) in multiethnic youth. The study was longitudinal involving 581 European American (EA) and African American (AA) youth with 12 assessments over a 15-year period. AGT M235T and three AGTR1 polymorphisms (C-521T, L191L and A1166C) were genotyped and individual growth curve modeling analyses were conducted. Single nucleotide polymorphism (SNP) analyses found a significant 3-way interaction between M235T, ethnicity and gender on BP levels. Systolic BP (SBP) levels were 5.8 mmHg ( p = .00003) and diastolic BP (DBP) levels were 2.6 mmHg ( p = .005) lower in carriers versus noncarriers of the M235 allele in AA males only. Furthermore, the AGTR1 L191 allele showed a SBP lowering effect in subjects with a high socioeconomic status (SES; p = .048) and a DBP lowering effect in AAs ( p = .038). Haplotype analyses identified a protective haplotype (C-521, 191L and A1166) for LVM levels ( p = .03). LVM in individuals homozygous for this haplotype was 12.9 g lower than those homozygous for the most common haplotype (–521T, 191L and A1166). No significant interactions were found between the AGT M235T polymorphism and any of the single SNPs or haplotypes of the AGTR1 gene. Our results in multiethnic youth uncover an ethnicity and gender-specific effect of the AGT M235T polymorphism and a SES or ethnicity-specific effect of the AGTR1 L191L polymorphism on the progression of hypertension risk. A protective AGTR1 haplotype for LVM was also identified.