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HYPERTENSION MARKER


CHARLESTON, S.C.- A newly identified gene polymorphism could lead to powerful tests to diagnose stroke risk in blacks, reported researchers at the 20th International Joint Conference on Stroke and Cerebral Circulation.

University of Texas researchers first identified 199 patients prone to stroke by using ultrasound to measure the thickness of carotid arteries. The researchers then searched for insertion/deletion polymorphisms in the ACE (angiotensin-converting enzyme) gene, which has been reported to be a risk factor for coronary artery disease and heart attack. After obtaining genomic DNA from all patients, the researchers used synthetic primers for the intron-16 region of the human ACE gene to locate selected polymorphisms via electrophoresis and PCR.

Seventy percent of the black patients in the survey shared a common ACE gene mutation, marked by a deletion/deletion polymorphism. No significant correlation was found in the Caucasian patients reported study director Dr. Frank Yatsu, professor and chairman of the department of neurology, University of Texas health Science Center, Houston, TX.

"This study suggests that determination of ACE gene polymorphism for the African-American population may be a useful marker for identifying stroke-prone individuals before the occurrence of clinical episodes," said Dr. Yatsu.

The ACE gene directs the production of a key enzyme that converts angiotensin I into angiotensin II. Angiotensin II stimulates the walls of the blood vessels to contract, leading to an increase in blood pressure. High blood pressure is a major risk factor for subsequent stroke. This protein also causes smooth muscle cells in the vessel walls to proliferate and harden.

Public health authorities have long sought a biological markers for hypertension in blacks. Studies of the U.S. population conducted by the American Heart Association show that death rates for stroke are more than 100% higher among black males than white males and nearly 80% higher among black women.

The next step in the research will be to confirm the findings in a larger study. In addition to providing a useful early warning test for stroke risk, these findings also may provide a clue on the best therapeutic approach for blacks with hypertension. A study involving a class of drugs currently used to treat hypertension called ACE-inhibitors will probably be conducted in black patients, notes Dr. Yatsu.

Japanese researchers recently reported (Iwai et al., Circulation, 12/94) identified a gene encoding for angiotensin converting enzyme (ACE) which also appears to be an independent risk factor for left ventricular hypertrophy, an anatomic condition associated with heart failure. Researchers at Shiga University studied 268 individuals chosen at random from an outpatient clinic, using ultrasound to measure the size of the patients' left ventricles. They also performed polymerase chain reaction evaluations of genomic DNA (from peripheral leukocytes) to determine the patients ACE genotype. The study revealed that variations of the gene with two key deletions called the "DD genotype" were significant predictors of left ventricular hypertrophy..


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