Genetic Factors and Blood Pressure in African Americans

According to a press release from the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, researchers have found “five genetic variants related to blood pressure in African Americans” that may “provide new clues to treating and preventing hypertension” in African American patients. Roughly 40% of African American males and 43% of females are affected by hypertension.

The results were derived from a genome-wide association study (more on this below) that focused on blood pressure and hypertension in an African American population, one of the first times this approach was used to study these conditions in this patient population. Eric Green, MD, PhD, scientific director for the NHGRI, said that “This work underscores the value of using genomic tools to untangle the complex genetic factors that influence the risk for hypertension and other common diseases.” Green also said that “We hope these findings eventually will translate into better ways of helping the millions of African-Americans at risk for hypertension, as well as improved treatment options for other populations.”

The study “A Genome-wide Association Study of Hypertension and Blood Pressure in African Americans” was recently published online in PLoS Genetics.

The authors reported “sought genetic variants underlying blood pressure (BP) by conducting a genome-wide association study (GWAS) among African Americans, a population group in the United States that is disproportionately affected by hypertension and associated complications, including stroke and kidney diseases.” Researchers used “a dense panel of over 800,000 [single-nucleotide polymorphisms] SNPs in a discovery sample of 1,017 African Americans” (half of whom had been diagnosed with hypertension) and identified “multiple SNPs reaching genome-wide significance for systolic BP in or near the genes: PMS1, SLC24A4, YWHA7, IPO7, and CACANA1H.”

According to the NHGRI press release, these five genetic variants were found “significantly more often in people with hypertension than in those without the condition,” and “were associated with high systolic blood pressure, but not with diastolic blood pressure or combined systolic/diastolic blood pressure.”

In the published study results in PLoS Genetics, the authors noted that “Two of these genes, SLC24A4 (a sodium/potassium/calcium exchanger) and CACNA1H (a voltage-dependent calcium channel), are potential candidate genes for BP regulation and the latter is a drug target for a class of calcium channel blockers.”

Senior study author Charles Rotimi, PhD, NHGRI senior investigator and director of the trans-NIH Center for Research on Genomics and Global Health (CRGGH), said that “Although the effect of each individual genetic variant was modest, our findings extend the scope of what is known generally about the genetics of human hypertension.”

The NHGRI press release noted that “all of the five genetic variants associated with blood pressure were located in or near genes that code for proteins thought to be biologically important in hypertension and blood pressure. Previous research had implicated two of those genes in blood pressure regulation, and additional analyses by Dr. Rotimi’s group revealed that all of the variants are likely involved in biological pathways and networks related to blood pressure and hypertension.”

In their discussion of the study results in PLoS Genetics, the authors said that their findings “provide a set of candidate genes to be evaluated in-depth in future studies. Further replication and fine mapping in multiple populations, especially in an independent African American samples, are needed.” These results, coupled with what the authors describe as “the global lack of success in identifying susceptibility loci for essential hypertension using genome-wide linkage and association strategies,” led the authors to conclude that “the genetic architecture underlying BP control must be considerably more complex and sufficiently different from those of other common complex human diseases (eg, diabetes).” This may be why the current agnostic approaches of searching the genome of thousands of individuals for risk loci have “not yielded strong and consistent results for hypertension and BP.”

What is a Genome-wide Association Study?

Click here for more information from the NHGRI about genome-wide association studies and links to additional resources.