Pathological Significance of Gene Polymorphisms of the Renin-Angiotensin System in Hypertension.

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The renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure and regional blood flow. Gene polymorphisms of 3 major components of the RAS, angiotensinogen, angiotensin converting enzyme (ACE) , and angiotensin II type 1 receptor (AT1R) have been raised as possible genetic markers for hypertension and its complications. The mortality and morbidity of hypertension and hypertensive cardiovascular diseases are high in the Aomori population. Therefore, we tried to identify the prevalence of significant 3 gene variants of those components in hypertensive and normotensive subjects living in Aomori prefecture. Patients with end-stage renal disease (ESRD) and patients with cerebrovascular diseases were also enrolled in this study. Positive linkages were identlfied between hypertension and 2 gene polymorphisms including angiotensinogen M235T and ACE I/D. However, disequilibriums in AT1R A1166C polyrrmorphism was absent between hypertensive and normotensive groups. ACE I/D was also associated with cerebrovascular diseases, but not with ESRD.These results suggest that the angiotensinogen M235T and ACE I/D variants may be genetic-susceptibility factors for hypertension and that ACE I/D may further contribute to cerebrovascular diseases as a genetic marker in the Aomori population.