A slim, middle-aged, non-smoking vegetarian with normalblood pressure and cholesterol levels suffers a severe heartattack. How did he go wrong?
By having parents with a missing DNA sequence in the genethat codes for angiotensin converting enzyme (ACE), suggestsFrench research cardiologist Franois Cambien. A four-center,case-controlled study of 1,343 European men, reported inNature on Thursday, bears the tell-all title, "Deletionpolymorphism in the gene for angiotensin --converting enzymeis a potent risk factor for myocardial infarction."
It found that men who had a myocardial infarction were morelikely to have been born with a variation in their ACE-encodinggene than those who had not.
ACE acts by switching on angiotensin II, a hormone thatconstricts blood vessels to keep the body's circulation inbalance. But synthesizing too much ACE is thought to contributeto cardiovascular disease, and "ACE inhibitors have spectacularsuccess in treating heart attacks," said molecular geneticistTheodore W. Kurtz of the University of California School ofMedicine. Kurtz titled his commentary in Nature on Cambien'sreport "The ACE of hearts."
Research cardiologist Cambien is at France's National Instituteof Medical Research (INSERM) in Paris. His population study, atthree geographically separated French medical centers, plusBelfast, Northern Ireland, used polymerase chain reaction (PCR)DNA amplification to compare the genomes of 610 heart attacksurvivors (at high risk of a second heart attack) with 733matched healthy controls.
The former were three times as likely as the controls to have anon-coding stretch of DNA on intron 16 of the ACE gene missingfrom both parental strands of the double helix. The deletionpolymorphism occurs in 27 percent of the general population.
This new high-risk indicator for heart disease was independentof the usual suspects: smoking, obesity, plasma lipid andcholesterol profiles, and blood pressure. In other words, asCambien proposed, the double deletion "might be particularlyimportant in myocardial infarction patients considered to be atlow risk according to the usual criteria."
His report ends, "As with any newly proposed risk factor,independent confirmation of our results will be necessary."
"I'm sure someone will do so very quickly.," Kurtz told toBioWorld. "Meanwhile, no one is advocating using it as ascreening test in the general population," he added.
"The aberrant intron deletion is only one of many genetic riskfactors," Kurtz emphasized, "and may be merely a markerpointing to some entirely different DNA sequence variant,perhaps as much as 500 kilobase pairs nearer to the ACE genelocus. "
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.