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Angiotensinogen polymorphisms and elevated blood pressure in the general population: the Copenhagen City Heart Study
A A Sethi1, B G Nordestgaard, B Agerholm-Larsen
1Department of Clinical Biochemistry, Herlev University Hospital, Herlev, Denmark.
Insights
Certain angiotensinogen gene mutations (Thr235 and Thr174) increase angiotensinogen levels. Double homozygosity for Thr235 and Thr174 is a risk factor for elevated blood pressure in women, but not men.
Area of Science:
- Genetics and cardiovascular health
- Population genetics and hypertension
Background:
- Elevated blood pressure (hypertension) is a major risk factor for cardiovascular disease.
- The angiotensinogen gene plays a crucial role in the renin-angiotensin-aldosterone system, regulating blood pressure.
- Specific gene mutations may influence angiotensinogen levels and predispose individuals to hypertension.
Purpose of the Study:
- To investigate the association between Met235Thr and Thr174Met mutations in the angiotensinogen gene and elevated blood pressure.
- To determine if these mutations impact plasma angiotensinogen levels and blood pressure parameters in a general population.
Main Methods:
- Genotyping of 9100 individuals from the Danish general population for angiotensinogen gene mutations (Thr235 and Met174).
- Statistical analysis using multifactorial logistic regression to assess the relationship between genotypes and elevated blood pressure.
- Measurement of plasma angiotensinogen levels and correlation with blood pressure parameters.
Main Results:
- Women homozygous for Thr235 had a higher odds ratio for elevated blood pressure (1.29), increasing to 1.50 if also homozygous for Thr174.
- Increased risk of isolated elevated systolic blood pressure and mild blood pressure elevation was observed in women with Thr235 homozygosity.
- No significant association was found between genotypes and elevated blood pressure in men.
- Homozygosity for Thr235 and Thr174 correlated with a 10% increase in plasma angiotensinogen levels in both genders, but only women showed a positive correlation between blood pressure and angiotensinogen levels.
Conclusions:
- Double homozygosity for Thr235 and Thr174 in the angiotensinogen gene is associated with increased plasma angiotensinogen levels.
- This genetic profile represents a significant risk factor for elevated blood pressure specifically in women.
- The findings highlight gender-specific genetic influences on hypertension risk within the renin-angiotensin-aldosterone system.
Abstract:
In the present study, we tested the hypothesis that the Met235Thr and Thr174Met mutations were associated or not with elevated blood pressure. We genotyped 9100 women and men from the Danish general population, of whom 54% had 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 analysis, women homozygous for Thr235 versus noncarriers had an odds ratio for elevated blood pressure of 1.29 (95% CI 1.05 to 1.58), which increased to 1.50 (1.15 to 1.96) if they also were homozygous for Thr174 (noncarrier of Met174). Women homozygous for Thr235 also had an increased risk of isolated 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 significant association between elevated blood pressure and genotype in men or among genotype and systolic blood pressure, diastolic blood pressure, or pulse pressure in either gender. Homozygosity for both Thr235 and Thr174 was associated with a 10% increase in plasma angiotensinogen levels in both genders compared with homozygosity for Met235 and Thr174; however, systolic and diastolic blood pressures were positively correlated to plasma angiotensinogen levels in women only. In conclusion, in this large-scale study of the general population, double homozygosity for Thr235 and Thr174 in the angiotensinogen 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.