Impact of renin-angiotensin-aldosterone system gene variants on the severity of hypertension in patients with newly diagnosed hypertension.
BACKGROUND
The severity of hypertension has prognostic significance. Previous studies have assessed the relationship between renin-angiotensin-aldosterone system (RAAS) genotype and the severity of hypertension in either treated patients or those who have only recently discontinued treatment.


METHODS
We assessed the impact of RAAS genotype on ambulatory and office blood pressure (BP) in 231 newly diagnosed hypertensive patients of African ancestry who had never received therapy. Subjects were genotyped for variants of the angiotensin-converting enzyme (insertion/deletion), angiotensinogen (M235T, -20A-->C), and aldosterone synthase (CYP11B2)(-344C-->T) genes.


RESULTS
The CYP11B2 gene polymorphism was associated with systolic BP (SBP). In comparison to subjects with at least one copy of the -344C allele (n = 75), patients who were homozygous for the -344T allele (n = 156) had both higher ambulatory SBP (150 +/- 1 v 144 +/- 1 mm Hg, P =.002 before and P =.01 after adjusting for multiple genotyping) and office SBP (163 +/- 2 v 156 +/- 2 mm Hg, P =.01 before and P =.05 after adjusting for multiple genotyping). Neither the angiotensin-converting enzyme insertion/deletion nor the angiotensinogen gene polymorphisms were associated with ambulatory or office SBP or diastolic BP (DBP). The CYP11B2 gene variant also did not affect DBP.


CONCLUSIONS
A variant within the CYP11B2 locus has a clinically important impact on the severity of SBP changes in individuals with newly diagnosed hypertension who are of African ethnicity.
Tiago
Armindo D
AD
Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand, Parktown, Johannesburg, South Africa.
Badenhorst
Danelle
D
Nkeh
Benedicta
B
Candy
Geoffrey P
GP
Brooksbank
Richard
R
Sareli
Pinhas
P
Libhaber
Elena
E
Samani
Nilesh J
NJ
Woodiwiss
Angela J
AJ
Norton
Gavin R
GR
D000808:Angiotensinogen / Q000235:genetics / Q000502:physiology; D044383:Black People / Q000235:genetics*; D018660:Blood Pressure Monitoring, Ambulatory; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics* / Q000502:physiology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000502:physiology; D012084:Renin-Angiotensin System / Q000235:genetics* / Q000502:physiology; D012720:Severity of Illness Index; D013019:South Africa
D000808:Angiotensinogen; D019405:Cytochrome P-450 CYP11B2; D007703:Peptidyl-Dipeptidase A