Hypertension is a major risk factor for cardiovascular disease, stroke, and end-stage renal disease61. In 2005 the prevalence of hypertension of the adult population worldwide was 26% 62. Blood pressure is higher in men compared to women among adults under the age of 45, but this trend switches and at 70−79 years of age women have higher blood pressure than men63,64, similar to overall trends for cardiovascular disease (Figure 1). Genes involved in the renin-angiotensinogen system are functional candidates for blood pressure regulation and hypertension, and have been associated with these phenotypes with varying success (reviewed in Kato et al.65). A 250 bp deletion/insertion (D/I) polymorphism in intron 16 of the angiotensin converting enzyme (ACE) gene accounts for approximately 47% of the variance in plasma ACE protein levels, with each copy of the D allele associated with an approximately 30% increase in ACE levels66. ACE was considered a candidate gene for blood pressure and hypertension, but results of case–control association studies with blood pressure were conflicting and family-based studies failed to demonstrate linkage between the ACE locus and hypertension (ref.50 and references therein).
