Variants and Haplotypes in Angiotensinogen Gene Are Associated With Plasmatic Angiotensinogen Level in Mexican Population

Introduction: The plasmatic angiotensinogen (AGT) level has been associated with essential hypertension. Linkage analysis has found a relationship between the AGT gene locus and hypertension in the Mexican-American population, but studies have failed to identify genetic variants associated with hypertension or plasma AGT levels. This study analyzes the relationship between polymorphisms in the AGT gene and plasmatic AGT levels in Mexican population. Methods: Nine polymorphisms in AGT gene were geno-typed, and plasma AGT level was determined by enzyme-linked immunosorbent assay. Results: Differences in AGT plasma levels were associated with 2 polymorphisms: T-20G, TT = 25.3 +/- 8.3 versus TG + GG = 21.6 +/- 8.8 mu g/mL; P = 0.008 and C3389T (T174M), CC = 25.8 +/- 9.9 versus TC + TT = 20.5 +/- 5.4 mu g/mL; P = 0.0002. Haplotype 2 was associated with low plasma AGT (-5.1 mu g/mL [95% confidence interval: -8.6 to -1.6], P = 0.004) and Haplotype 8 was associated with high plasma AGT (6.5 mu g/mL [95% confidence interval: 2.5 to 10.6], P = 0.001). This association remained after adjustment for covariates. A Likelihood Ratio Test for haplotype-phenotype association adjusted for covariates resulted in chi(2) = 38.9, P = 0.0005. The total effect of the haplotypes on plasma AGT level variance was 19.5%. No association was identified between haplotypes and quantitative traits of blood pressure. Conclusions: Two polymorphisms (T-20G and C3389T) and 2 haplotypes (H2 and H8) showed an association with plasma AGT levels in Mexican population.