A genetic mutation that slows the rate that the body metabolizes caffeine increases individuals’ risk of having a heart attack if they drink much coffee, investigators report in the Journal of the American Medical Association.

Caffeine is metabolized primarily in the liver by the cytochrome P450 1A2 (CYP1A2) enzyme, Dr. Ahmed El-Sohemy and colleagues note. They explain that mutation in the gene that codes for this enzyme alters the rate of caffeine metabolism. This may explain why studies looking at the association between coffee consumption and heart attack risk have been inconclusive.

To test the effect of the CYP1A2 mutations on heart attack risk, El-Sohemy, from the University of Toronto, and his team mapped out the genes that result in slow metabolism and those that result in rapid metabolism for 2,014 patients who had a first nonfatal heart attack and for 2,014 healthy controls. The study was conducted between 1994 and 2004 in Costa Rica.

The team’s results showed that only carriers of the gene mutation for slow caffeine metabolism were at increased risk of heart attack associated with drinking coffee.

For these patients, the increased risk was 64 percent for four or more cups per day over the previous year compared with patients who drank less than one cup per day. The corresponding risk was less than 1 percent for subjects who had two copies of the rapid metabolizing gene.

These relationships were similar in nonsmokers and smokers.

The gene-coffee interaction was more pronounced among the younger subjects. For individuals younger than 50 years, the risk of heart attack associated with the slow-metabolizing gene was increased by four-fold for those who drank four or more cups per day compared with those who drank less than one cup a day. For subjects with two copies of the rapid metabolizing gene, the corresponding risk was less than 1 percent.

SOURCE: Journal of the American Medical Association, March 8, 2006.