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Gene variants linked with increased risk of death among heart patients treated with beta-blockers

Patients with certain gene variants who were prescribed beta-blocker drugs after acute coronary syndrome (ACS) had an increased risk of death over the next three years, according to a study in the September 28 issue of JAMA.

Beta-blockers are drugs that block the action of beta-adrenergic substances such as adrenaline in the "sympathetic" portion of the nervous system relieving stress on the heart, slowing the heartbeat, and reducing blood vessel contraction in the heart, brain, and throughout the body, according to background information in the article. Previous data support an association between variants of the ADRB1 and ADRB2 genes and response to beta-blocker therapy, but no relationship between these variants and the survival of patients receiving beta-blocker therapy has been reported.

David E. Lanfear, M.D., formerly of Washington University School of Medicine, St. Louis, and colleagues conducted a prospective cohort study of 735 ACS patients admitted to two medical centers between March 2001 and October 2002. The ACS patients were diagnosed with either myocardial infarction (heart attack) or unstable angina (an accelerating pattern of chest pain that lasts longer and is less responsive to medication than stable angina). Among those enrolled in the study, 597 were discharged from the hospital with beta-blocker therapy. DNA testing was conducted to find out if the patients carried any of four common variants of the ADRB1 and ADRB2 genes (ADRB1 1165 CG, 145 AG; ADRB2 46 GA, 79 CG).

The researchers followed the study patients for three years after discharge. There were 84 deaths during follow-up.

"There was a significant association between ADRB2 genotype and three-year mortality among patients prescribed beta blocker therapy," the authors report.

"For the 79 CG polymorphism, three-year mortality rates were 16 percent (35 deaths), 11 percent (27 deaths), and six percent (four deaths) for the CC, CG, and GG genotype
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Contact: Diane Duke Williams
314-286-0111
JAMA and Archives Journals
27-Sep-2005


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