D014: Angiotensinogen gene mutations and hypertension in the general population

• Published in: American journal of hypertension 2000-04, Vol.13 (S2), p.77A-78A
• Main Authors: Sethi, A.A., Nordestgaard, B.G., Agerholm-Larsen, B., Frandsen, E., Jensen, G., Tybjærg-Hansen, A.
• Format: Article
• Language: English
• Subjects: Angiotensinogen; genetics; hypertension; molecular variants
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1016/S0895-7061(00)00852-9

Hypertension is linked to the angiotensinogen gene. We tested the hypothesis that the Thr174Met and Met235Thr mutations in this gene increase the risk of hypertension. We genotyped 9100 women and men from the Danish general population, of which 54 percent had hypertension. Twelve and 41 percent carried the 174M and 235T mutations, respectively. The 174M mutation always occurred on the same allele as the 235T mutation. On multifactorial logistic regression analysis, women homozygous for 235T had an odds ratio for hypertension of 1.29 (95 percent confidence interval, 1.05 to 1.58), which increased to 1.50 (95 percent confidence interval, 1.15 to 1.96) if they in addition were homozygous for 174T. Women homozygous for 235T also had increased risk of isolated systolic hypertension (OR, 1.37; 95 percent confidence interval, 1.02 to 1.84), and of mild hypertension (OR, 1.40; 95 percent confidence interval, 1.10 to 1.77). Finally, women homozygous for both 235T and 174T had increased risk of being on antihypertensive medication (OR, 1.53; 95 percent confidence interval, 1.12 to 2.09). We found no effects on risk of hypertension as a function of genotype in men, and no significant differences on systolic- or diastolic blood pressure or pulse pressure as a function of genotype in either gender. The M235T mutation was associated with a 10 percent increase in levels of plasma angiotensinogen concentration in both genders, and explained 6 and 5 percent of the total variation in plasma angiotensinogen concentration in women and men, respectively. Systolic and diastolic blood pressure was positively correlated to plasma angiotensinogen concentration in women. In the homozygous state, 235T in the angiotensinogen gene increases plasma angiotensinogen concentration by 10 percent in either gender, and was a weak risk factor for hypertension in women, but not in men.