Genetic variants linked to higher risk of high blood pressure in African Americans

September 14, 1999

ORLANDO, Fla., Sept. 14 -- Researchers have identified two gene variants that may help explain why certain populations, such as African Americans, are at higher risk for high blood pressure than Caucasians.

The two studies presented at the American Heart Association's high blood pressure meeting may lead to new methods for diagnosing and treating high blood pressure.

"These results may help us to better understand high blood pressure, with potential long-range implications, including the development of early diagnostic tests and the design of more specific and effective drugs to treat this serious disease," says the study's lead author, Robert J. Parmer, M.D., professor of medicine at the University of California, San Diego (UCSD) and director of the Hypertension Clinic at the San Diego VA Medical Center.

In the study, researchers from UCSD and the Medical University of South Carolina found that variations in the human tissue kallikrein gene may govern the body's ability to regulate levels of an enzyme called renal kallikrein. The enzyme releases hormones called kinins, which dilate blood vessels and can affect salt and water balance in the body. Reduced renal kallikrein appears, in part, to be inherited and is associated with high blood pressure.

"It appears that an inherited abnormality in the kallikrein system, which reduces the amount of enzyme in the kidneys, may contribute to high blood pressure," Parmer says.

He and his colleagues measured the amount of kallikrein in urine and studied the human kallikrein gene in 296 people (169 whites and 127 blacks). They identified 13 different gene variations.

"One of the variants, "B", was associated with higher amounts of kallikrein levels in the urine and may offer a protective effect against high blood pressure," says Parmer. In fact, those with the B variant excreted 75 percent more kallikrein enzyme in their urine than those with other variants of the gene.

The B variant of the kallikrein gene was nearly three times more common in Caucasians (24 percent) than in African Americans (9 percent), suggesting a possible explanation of why blacks are at higher risk of developing high blood pressure than whites.

"These results suggest that variations in the kallikrein gene affect how much of the enzyme renal kallikrein is manufactured by the kidneys and may be a factor leading to high blood pressure in some individuals," Parmer says.

Another study by researchers in New York found that people with high blood pressure produce more of a substance called transforming growth factor (TGF)-beta 1 than those with normal blood pressure levels. And African Americans with high blood pressure tend to overproduce this substance more than Caucasians with high blood pressure.

African Americans develop high blood pressure at an earlier age than Caucasians. They also tend to have more severe high blood pressure than whites. As a result, blacks face an increased risk of stroke, heart disease and end-stage kidney failure.

African Americans are four times more likely than whites to develop kidney failure. African Americans are much more to suffer kidney failure as a consequence of high blood pressure.

"Approximately one of every four Caucasians between the ages of 20 to 74 has high blood pressure compared to one out of every three African Americans," says Phyllis August, M.D., professor of medicine and chief of the hypertension division at Weill Medical College of Cornell University in New York City.

Genetic factors are believed to play a role in these different racial susceptibilities to high blood pressure and organ damage.

The Cornell team's study, one of many it has performed in collaboration with M. Suthanthiran, M.D., a co-author of the study and an expert on TGF-beta 1, followed its earlier finding that blacks with kidney failure produced more of this growth factor than did whites with kidney failure. "So we wanted to look at TGF-beta 1 in hypertension," August says.

Researchers say that the amount of TGF-beta 1 a person produces may be determined by variations of the TGF-beta 1 gene. TGF-beta 1 is involved in creating scar tissue, which contributes to the progression of kidney failure.

The researchers studied groups of African Americans and Caucasians, both with and without high blood pressure. They found that blood levels of TGF-beta 1 were higher in blacks and whites with high blood pressure than in those with normal blood pressure. However, African Americans with or without high blood pressure had higher levels of TGF-beta 1 than their white counterparts.

Researchers measured a TGF-beta 1 messenger RNA, a substance that demonstrates if the gene is directing the cell to make TGF-beta protein. Researchers found that people with high blood pressure made more TGF-beta 1 messenger RNA than those with normal blood pressure and that blacks had higher levels than whites.

Finally, August and her colleagues found that the different amount of TGF-beta 1 messenger RNA correlated with different variations in the gene.

The Cornell team is now beginning a study to see if the TGF-beta 1 gene variants correlate with a higher risk of kidney failure and high blood pressure.

"We don't think that TGF-beta 1 is the cause of high blood pressure," August says. "However, the gene could be used to identify individuals who make too much of TGF-beta 1 and might benefit from a more aggressive approach. There are drugs now that can block TGF-beta 1 production." One such group of drugs currently used to control high blood pressure is A.C.E. inhibitors, which interfere with the body's production of angiotensin, a chemical that causes the arteries to constrict. Angiotensin also stimulates TGF-beta 1 production.

Co-authors with August are Baougui Li, Ph.D.; Ruching Ding, M.D.; Vijay K. Sharma, Ph.D.; J. O. Song, M.D.; and Geraldine Helseth, R.N. Co-authors with Parmer are Qing Song, Ph.D.; Mala T. Kailasam, M.M.D.; Daniel T. O'Connor, M.D.; Julie Chao, Ph.D.; and Lee Chao, Ph.D.

American Heart Association

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