Angiotensin-converting enzyme gene I/D polymorphism in malignant hypertension

Background: The mechanism of the rapid transition of a stable benign hypert ensive disease to a severe and devastating malignant hypertension is not fu lly understood. However, the renin angiotensin system, which is highly acti vated in malignant hypertension, is established as an important pathogeneti c factor in different cardiovascular and renal diseases. Over the last deca de, a polymorphism in gents regulating this system has been found. This inc ludes the 287 bp sequence deletion (D)/insertion (I) polymorphism in the an giotensin-converting enzyme (ACE) gene and the methionine (M) to threonine (T) Feint mutation polymorphism in the angiotensinogen (AGT) gene. These ge ne polymorphisms have been associated with various cardiovascular and renal diseases and the aim of this study was to investigate whether they were li nked to malignant hypertension. Methods Forty-two patients with malignant h ypertension (mean age 55 years), 32 patients with non-malignant hypertensio n (mean age 57 years) and 85 normotensive control subjects (mean age 42 yea rs) were investigated with respect to ACE I/D and AGT M/T genotypes. DNA ma s prepared by standard methods from isolated white blood cells and analysed by the PCR technique. The PCR reaction used in the detection of the ACE VD polymorphism was optimized for an equal amplification of the I and D allel es. Results: The frequency of the DD genotype was significantly increased i n patients with malignant hypertension (43%) compared with patients with no n-malignant hypertension (14%) and normotensive control subjects (18%) (p < 0.01) for both. The frequency distribution of AGT M/T genotype did not dif fer between patients with malignant and non-malignant hypertension. Conclus ion. The DD genotype of the ACE gene occurred more than twice as often in m alignant hypertension than in non-malignant hypertension and indicates that ACE gene polymorphism is a significant risk factor for initiation of malig nant hypertension.