From genomics to therapuetics: Highlight from the ABC 21st Annual Scientific Sessions

At the Association of Black Cardiologists (ABCs) 21st Annual Scientific Sessions, held in Chicago, Illinois, on March 29, 2008, Michelle A. Albert, MD, MPH, Assistant Professor of Medicine, Harvard Medical School, Associate Physician, Brigham and Women’s Hospital, Boston, Massachusetts, discussed the relationships between genes and the environment. She also provided a historical perspective of how diseases may manifest based on our current genetic profile. Dr Albert noted that genetic variance may influence cardiovascular disease, with inheritance patterns ranging from Mendelian (rare) diseases to complex (influenced by common polymorphisms) and polygenic diseases.

Mendelian disorders include familial hypercholesterolemia, which can be tracked within families using linkage analyses. While common disorders may have Mendelian components, cardiovascular diseases are complex and polygenic, usually involving polymorphisms that work in combination. Found in most human populations, and of ancient origin, these common polymorphisms are typically found in more than 1% of the population, whereas Mendelian inheritance patterns are usually found in less than 1%.

By most scientific analyses, modern human populations initially emerged from Africa between 100,000 and 150,000 years ago. Approximately 80,000 years ago, there appeared to be rapid environmental changes in Africa, which resulted in a major expansion of people from that small source area and, later, a dispersal of modern populations from Africa to Eurasia. Dr Albert discussed selected examples of gene-environmental interactions pertaining to cardiovascular disease, which may have been related to our diet and nutrition, exposure to environmental factors, as well as the genetic background found in Africa during this time.

In modern studies, such as the Framingham Heart Study, there appears to be a relationship between genes and the expression of dyslipidemia, typically in the form of elevated triglyceride levels. Nevertheless, polymorphisms for genes affected by dyslipidemia can be affected by body mass index (BMI) and monosaturated fat and caloric intake. For instance, subjects who are homozygous for the dominant allele for the apolipoprotein A5 gene and have a higher caloric intake will gain weight. This association is an example of the presence of the genetic variance, which can be affected by lifestyle.

Dr Albert went on to point out that obesity is not only a huge problem in the United States, but worldwide. Specifically, 75% of African American women are either overweight or obese, which is a considerable risk factor for developing cardiovascular disease and diabetes. Because of the distinct interaction between BMI, genes, and diet, she stressed the importance of ensuring that adults, particularly women, pay attention to body weight.

As far as hypertension is concerned, which is more common in African Americans, Dr Albert noted that multiple theories may impact our understanding of blood pressure and genetics. One theory suggests that the Middle Passage in the Atlantic slave trade self-selected for individuals who may have been prone to developing hypertension. There also may be differences in rural versus Westernized environments, although there are no clear genetic differences in polymorphisms in people living in rural Africa versus Westernized environments in Africa.

Dr Albert concluded that although definitive statements related to genes, environment, and cardiovascular disease are difficult to make given our current scientific knowledge, several points should be kept in mind. First, humans have 1 ancestral origin in Africa, which probably influences disease susceptibility. Second, the magnitude of gene-environment interactions determines disease development and phenotypic expression. Moreover, there are some particularly difficult-to-quantify factors related to social and racial disparities, including neighborhood environments and racism. Finally, large prospective studies in diverse populations are optimal. Although such studies are expensive and time-consuming, they may provide fertile ground to move forward in understanding gene-environment interactions in a prospective manner.