Geographic Ancestry, Angiotensinogen Gene Polymorphism, and Cardiovascular Risk

Abstract

The influence of race on the association of genetic variants with pathological phenotypes is an intriguing issue, and the study by Goldenberg et al1 published in the present issue of Hypertension stimulates several considerations. The concept of “race” itself is the object of major controversy between those claiming that there is no biological basis for it and others supporting the scientific validity of pragmatic racial categorizations, such as that proposed by the Office of Management and Budget in the United States. Without fear of appearing “politically incorrect,” we should admit that the analysis of a large set of genetic markers has convincingly shown that ≈10% of total genetic variation in humans originates from differences between a limited number of population groups, corresponding to “geographic clusters” of individuals.2 Race or, perhaps better, ancestry-related genetic variability, may underline different genetic risk for 2 main reasons: (1) a susceptibility variant has different frequencies in individuals of different geographic ancestries or (2) a genetic variant may result associated with increased risk of disease in ≥1 population but not in individuals of different geographic ancestries. As a general consideration, a relevant proportion of genetic polymorphisms have a substantially different frequency in different population groups; in particular, common single nucleotide polymorphisms are frequently not shared between black and nonblack populations.2 On the other hand, …