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Gene Variation May Increase Risk of Heart Attack in Coffee Drinkers

March 7, 2006

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Individuals who have a genetic variation associated with slower caffeine metabolism appear to have an increased risk of non-fatal heart attack associated with higher amounts of coffee intake, according to a study in the March 8 issue of JAMA.

Previous studies examining the association between coffee consumption and risk of heart attack, or myocardial infarction, have been inconclusive. Coffee is a major source of caffeine, which is the most widely consumed stimulant in the world and has been implicated in the development of cardiovascular diseases.

However, coffee contains a number of other chemicals that have variable effects on the cardiovascular system. It is not clear whether caffeine alone affects the risk of heart attack or whether other chemicals found in coffee may be responsible. Caffeine is metabolized primarily by the enzyme cytochrome P450 1A2 (CYP1A2) in the liver.

Variations of the gene for this enzyme can slow or quicken caffeine metabolism. Carriers of the gene variant CYP1A2*1F allele are "slow" caffeine metabolizers, while individuals with the gene variant CYP1A2*1A allele are "rapid" caffeine metabolizers.

Ahmed El-Sohemy, Ph.D., of the University of Toronto, and colleagues conducted a study to determine whether gene variations of CYP1A2 modifies the association between consumption of caffeinated coffee and risk of nonfatal heart attack.

The study included 2,014 case patients with a first acute nonfatal heart attack and 2,014 controls, living in Costa Rica between 1994 and 2004. The genotypes of the participants were determined. A food frequency questionnaire was used to assess the intake of caffeinated coffee.

Fifty-five percent of cases and 54 percent of controls were carriers of the slow gene variant. Those carriers who drank 2 to 3 cups of coffee a day had 36 percent increased odds of heart attack; those who drank 4 or more cups per day had a 64 percent increased odds of heart attack.

Corresponding consumption for individuals with the rapid gene variant resulted in the reduced odds of heart attack by 22 percent and 1 percent, respectively.

Among the slow metabolizers, younger individuals showed an increased risk. The risk associated with drinking 4 cups per day or more compared with less than 1 cup per day increased from 2-fold for individuals younger than 59 years to more than 4-fold for those younger than 50 years.

Among the fast metabolizers who were younger than 59 years of age, those who drank 1 cup per day or 2 to 3 cups per day had a reduced odds of a heart attack by 52 percent and 43 percent, respectively.

"In summary, consistent with most case-control studies, we found that increased coffee intake is associated with an increased risk of nonfatal MI. The association between coffee and MI was found only among individuals with the slow CYP1A2*1F allele, which impairs caffeine metabolism, suggesting that caffeine plays a role in the association," the authors conclude.

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