The M235T polymorphism in the angiotensinogen gene is associated with the risk of malignant hypertension in white patients.
BACKGROUND
Malignant hypertension can be considered an extreme phenotype of renin-mediated hypertension. Therefore, we compared the allelic frequencies of the angiotensinogen (AGT) M235T, angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensin II-type I receptor (AT1R) A1166C polymorphisms in malignant hypertensive patients with hypertensive and normotensive controls.


METHODS
A total of 101 consecutive patients between 1995 and 2005 admitted to a large university hospital fulfilled the criteria for malignant hypertension. Seventy-five patients (74%) were compared with 150 hypertensive and 150 normotensive controls, randomly selected from a population study and individually matched on age, sex and ethnicity.


RESULTS
The odds of malignant hypertension in white subjects with the TT genotype of the AGT M235T polymorphism was 14.3 (5.5-37) compared to hypertensive controls, and 9.4 (3.8-23.2) compared to normotensive controls. Adjustment for age, sex, smoking and antihypertensive therapy did not affect this association. The association of AGT M235T with malignant hypertension was not significant in blacks. In patients with malignant hypertension, the TT genotype was associated with more severe renal dysfunction and microangiopathic haemolysis. No differences were found in allele frequencies of the ACE I/D or the AT1R A1166C polymorphisms between study groups.


CONCLUSIONS
The TT genotype of AGT M235T is associated with malignant hypertension in whites, carriers having an odds of approximately 10 to 1 compared to hypertensive and normotensive controls. These observations may provide a better understanding of the pathophysiology of malignant hypertension and offer possibilities for identifying patients at risk. Larger association or linkage studies are needed for a more detailed risk assessment.
van den Born
Bert-Jan H
BJ
Department of Internal and Vascular Medicine, Academic Medical Centre, Amsterdam The Netherlands. b.j.vandenborn@amc.uva.nl
van Montfrans
Gert A
GA
Uitterlinden
Andre G
AG
Zwinderman
Aeilko H
AH
Koopmans
Richard P
RP
D000328:Adult; D000368:Aged; D000808:Angiotensinogen / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006974:Hypertension, Malignant / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk
D000808:Angiotensinogen