Association of the angiotensinogen gene to serum angiotensinogen in blacks and whites

Laura J. Bloem, Tatiana Foroud, Walter T. Ambrosius, Mark P. Hanna, Duane A. Tewksbury, J. Howard Pratt

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

A variant of the angiotensinogen gene (AGT) that encodes for threonine at codon 235 (T235) has been associated with a higher serum angiotensinogen concentration and with hypertension in white subjects. The frequency of T235 is about two times higher in blacks than whites, suggesting that AGT may contribute to the susceptibility to hypertension in blacks more than it does in whites. However, an association of T235 with angiotensinogen level or blood pressure has not been observed in blacks, possibly because the high prevalence of T235 makes it insufficiently informative as a marker. For this reason, we undertook to further differentiate the T235 carrier state by constructing haplotypes with alleles in the 5' upstream region of AGT. One such haplotype, -1074t;T235, showed a significant association with angiotensinogen level in a cohort of black and white children and adolescents (76 blacks, mean age=12.3±2.0 [SD] years; 139 whites, mean age=12.4±1.8 years). With a linear regression model, the level of serum angiotensinogen was significantly related to body mass index (P=.0017) and the haplotype (P=.0001). Within specific race groups, the haplotype was significantly related to serum angiotensinogen in both the blacks (P=.0277) and whites (P=.0001). The mean level of angiotensinogen was higher in the blacks carrying a single copy of the haplotype than in those without the haplotype (1472.2±68.4 versus 1274.9±46.7 nmol angiotensin I/L), a difference that was marginally significant (P=.0609). In the whites, the level of angiotensinogen was also higher in carriers of a single copy than in those with no copy (1527.9±71.2 versus 1099.2±20.1 nmol angiotensin I/L) (P=.0003). Serum angiotensinogen level did not increase with two copies of the haplotype, but in each racial group, there were only four individuals who were homozygous. The haplotype showed a marginally significant relation (P=.0757) to the mean of longitudinally determined diastolic pressures adjusted for body mass index, race, sex, and age. In summary, using a haplotype to differentiate further the T235 carrier state, we observed an association of genotype with serum angiotensinogen level and blood pressure in blacks and whites. The findings suggest that AGT may play an important role in blood pressure regulation in both racial groups.

Original languageEnglish
Pages (from-to)1078-1082
Number of pages5
JournalHypertension
Volume29
Issue number5
StatePublished - May 1997

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Angiotensinogen
Haplotypes
Serum
Genes
Blood Pressure
Carrier State
Angiotensin I
hydroquinone
Linear Models
Body Mass Index
Hypertension
Threonine
Codon

Keywords

  • angiotensinogen
  • angiotensinogen genes
  • blood pressure
  • haplotypes
  • race

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Bloem, L. J., Foroud, T., Ambrosius, W. T., Hanna, M. P., Tewksbury, D. A., & Pratt, J. H. (1997). Association of the angiotensinogen gene to serum angiotensinogen in blacks and whites. Hypertension, 29(5), 1078-1082.

Association of the angiotensinogen gene to serum angiotensinogen in blacks and whites. / Bloem, Laura J.; Foroud, Tatiana; Ambrosius, Walter T.; Hanna, Mark P.; Tewksbury, Duane A.; Pratt, J. Howard.

In: Hypertension, Vol. 29, No. 5, 05.1997, p. 1078-1082.

Research output: Contribution to journalArticle

Bloem, LJ, Foroud, T, Ambrosius, WT, Hanna, MP, Tewksbury, DA & Pratt, JH 1997, 'Association of the angiotensinogen gene to serum angiotensinogen in blacks and whites', Hypertension, vol. 29, no. 5, pp. 1078-1082.
Bloem LJ, Foroud T, Ambrosius WT, Hanna MP, Tewksbury DA, Pratt JH. Association of the angiotensinogen gene to serum angiotensinogen in blacks and whites. Hypertension. 1997 May;29(5):1078-1082.
Bloem, Laura J. ; Foroud, Tatiana ; Ambrosius, Walter T. ; Hanna, Mark P. ; Tewksbury, Duane A. ; Pratt, J. Howard. / Association of the angiotensinogen gene to serum angiotensinogen in blacks and whites. In: Hypertension. 1997 ; Vol. 29, No. 5. pp. 1078-1082.
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N2 - A variant of the angiotensinogen gene (AGT) that encodes for threonine at codon 235 (T235) has been associated with a higher serum angiotensinogen concentration and with hypertension in white subjects. The frequency of T235 is about two times higher in blacks than whites, suggesting that AGT may contribute to the susceptibility to hypertension in blacks more than it does in whites. However, an association of T235 with angiotensinogen level or blood pressure has not been observed in blacks, possibly because the high prevalence of T235 makes it insufficiently informative as a marker. For this reason, we undertook to further differentiate the T235 carrier state by constructing haplotypes with alleles in the 5' upstream region of AGT. One such haplotype, -1074t;T235, showed a significant association with angiotensinogen level in a cohort of black and white children and adolescents (76 blacks, mean age=12.3±2.0 [SD] years; 139 whites, mean age=12.4±1.8 years). With a linear regression model, the level of serum angiotensinogen was significantly related to body mass index (P=.0017) and the haplotype (P=.0001). Within specific race groups, the haplotype was significantly related to serum angiotensinogen in both the blacks (P=.0277) and whites (P=.0001). The mean level of angiotensinogen was higher in the blacks carrying a single copy of the haplotype than in those without the haplotype (1472.2±68.4 versus 1274.9±46.7 nmol angiotensin I/L), a difference that was marginally significant (P=.0609). In the whites, the level of angiotensinogen was also higher in carriers of a single copy than in those with no copy (1527.9±71.2 versus 1099.2±20.1 nmol angiotensin I/L) (P=.0003). Serum angiotensinogen level did not increase with two copies of the haplotype, but in each racial group, there were only four individuals who were homozygous. The haplotype showed a marginally significant relation (P=.0757) to the mean of longitudinally determined diastolic pressures adjusted for body mass index, race, sex, and age. In summary, using a haplotype to differentiate further the T235 carrier state, we observed an association of genotype with serum angiotensinogen level and blood pressure in blacks and whites. The findings suggest that AGT may play an important role in blood pressure regulation in both racial groups.

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