Angiotensinogen polymorphisms and elevated blood pressure in the general population - The Copenhagen City Heart Study

In the present study, we tested the hypothesis that the Met235Thr and Thr17 4Met mutations were associated or not with elevated blood pressure. We geno typed 9100 women and men from the Danish general population, of whom 54% ha d elevated blood pressure. Of the 9100, 41% and 12% carried the Thr235 and Met174 mutations, respectively; the Met174 mutation always occurred on the same allele as the Thr235 mutation. On multifactorial logistic regression a nalysis, women homozygous for Thr235 versus noncarriers had an odds ratio f or elevated blood pressure of 1.29 (95% CI 1.05 to 1.58), which increased t o 1.50 (1.15 to 1.96) if they also were homozygous for Thr174 (noncarrier o f Met174). Women homozygous for Thr235 also had an increased risk of isolat ed elevated systolic blood pressure (1.37; 1.02 to 1.84) and of mild blood pressure elevation (1.40; 1.10 to 1.77). We found no statistically signific ant association between elevated blood pressure and genotype in men or amon g genotype and systolic blood pressure, diastolic blood pressure, or pulse pressure in either gender. Homozygosity for both Thr235 and Thr174 was asso ciated with a 10% increase in plasma angiotensinogen levels in both genders compared with homozygosity for Met235 and Thr174; however, systolic and di astolic blood pressures were positively correlated to plasma angiotensinoge n levels in women only. In conclusion, in this large-scale study of the gen eral population, double homozygosity for Thr235 and Thr174 in the angiotens inogen gene is associated with a 10% increase in angiotensinogen levels and is a risk factor for elevated blood pressure in women but not in men.