Genetics key to African-Americans' hypertension
BY AMY ADAMS
National health records have shown that African-Americans are more prone to high blood pressure than Caucasians, but pinning down the roots of that difference has proven elusive. Now, researchers at the School of Medicine have narrowed down the search for genes that contribute to this difference in disease risk.
Finding such a gene could have several benefits for African-Americans and other ethnic groups. One is that by knowing the normal role of the gene, doctors can better understand the disease and devise new drugs or treatments to keep blood pressure under control. It could also lead to genetic tests to help identify people at higher risk of heart disease.
The work takes advantage of genetic differences between people of African and European descent to home in on the location of the gene or genes. Future research will be needed to pinpoint exactly which genes in these regions are the culprit in heart disease risk.
“These regions have hundreds of genes, so it will take some time to whittle it down,” said Neil Risch, PhD, a UCSF geneticist who did the work while he was a professor of genetics at Stanford. The study by Risch, Xiaofeng Zhu, PhD, at Loyola University Medical Center, and other colleagues was published in Sunday’s online issue of Nature Genetics.
The study examined people with high blood pressure, a disease that kills roughly 50,000 people nationwide each year. People with this condition are more prone to heart attacks, strokes and kidney damage.
Doctors have known for many years that in the United States people of African descent are more likely to develop high blood pressure—also called hypertension—than people of European or Asian descent, but it hasn’t been clear how much of that risk is due to differences in diet, exercise, socioeconomic status, genetics or a combination of these factors.
Risch and his colleagues got to the heart of the question with the help of 270 known genetic differences between people of African and European descent. These genetic differences aren’t necessarily in genes. Instead, they are simply signposts on the chromosomes that indicate that a stretch of DNA is African in origin rather than European.
Most African-Americans have a mixed background with some European ancestry and therefore contain a mixture of African and European signposts at these locations. The goal was to figure out if people with high blood pressure were more likely to have the African or European version of these 270 differences. People in the study were participants in the U.S. National Heart, Lung and Blood Institute’s Family Blood Pressure Program.
This strategy highlighted regions near two of the signposts, one on chromosome 6 and the other on chromosome 21. In both cases, African-Americans with high blood pressure were more likely to have the African version of the signpost. According to Risch, chances are that the people with high blood pressure also have the African version of a gene in that region that increases their chances of developing high blood pressure.
Risch said the very fact that this type of analysis could turn up regions of interest is exciting. “This will raise a big discussion about how well a genome-wide analysis that is based on ancestry will work when you are dealing with a complex disease,” he said. Until this was completed, some people doubted that the intertwined risk factors of diet, exercise and genetics could be unraveled.
A large task still remains. In addition to finding the genetic culprit, there’s still the problem of figuring out how that gene increases high blood pressure risk. Does it simply enhance problems caused by a bad diet, or would the gene alone cause hypertension even in a person who exercises regularly?
Even with these unresolved questions, Risch said the study is a first step towards an answer to why African-Americans are more prone to high blood pressure.
Hua Tang, PhD, a Stanford graduate student now at the Fred Hutchinson Cancer Research Institute, also participated in the study.
This is the first of two stories on new research by Neil Risch, PhD, a former professor of genetics, that provides a deeper understanding of the relationship between race and genetics. Next week’s Medical Center Report will cover another of his studies, which is to be published in the February issue of the American Journal of Human Genetics.