Polymorphisms of the renin-angiotensin system in patients with multifocal renal arterial fibromuscular dysplasia

Fibromuscular dysplasia (FMD) is an important cause of renal artery stenosi s, particularly in young females. Polymorphisms of the renin-angiotensin (R A) system have been implicated in the pathogenesis of hypertension and athe rosclerotic vascular disease, and may play a role in the development of FMD . Examination of polymorphisms by PCR for angiotensin-converting enzyme (AC E) I/D, angiotensin II type 1 receptor (AT(1)R) A1166C and angiotensinogen (AGT) M235T and T174M was undertaken in 43 patients with typical multifocal renal arterial FMD (MF-FMD) and in 89 controls. The age of NIF-FMD patient s at the time of diagnosis of hypertension did not differ (38.6 + 11.1 year s vs 35.5 +/- 10.3 years, P = 0.12) from controls and the proportion (95% v s 86%, P = 0.14) of females was similar. Allele frequencies did not differ significantly between groups, except that MF-FMD patients had a significant ly higher frequency of the ACE I allele than control subjects (0.62 vs 0.47 , P = 0.026). Since the ACE I allele is associated with lower circulating A CE levels and possibly lower tissue levels of angiotensin II (Ang II), and since Ang II modulates vascular smooth muscle cell growth and synthetic act ivity, the I allele might predispose to defective remodelling of the arteri al media, and thus to the development of MF-FMD. This contrasts with athero sclerotic renal artery stenosis, coronary stent restenosis and carotid inti mal thickening, which are diseases affecting the arterial intima, and which are associated with increased frequency of the D allele.