Caffeine, genetic variation and risk of myocardial infarction.
Published: 2006
Language: eng
Number of pages: 164
ISBN-13: 9780494219942
Description: Epidemiological studies examining the association between coffee and myocardial infarction (MI) remain inconclusive. Coffee is a major source of caffeine and has been implicated in the development of cardiovascular diseases. Caffeine is metabolized by cytochrome P450 (CYP)1A2, and the physiological effects of caffeine are mediated through blockade of adenosine receptors. A genetic polymorphism in CYP1A2 (-163C>A) decreases enzyme inducibility resulting in slow caffeine metabolism, and a polymorphism in  ADORA2A (1083C>T) is associated with caffeine-induced anxiety. The overall objective of this research was to determine whether genetic differences in caffeine metabolism and sensitivity modify the association between coffee consumption and risk of MI. The hypothesis was that individuals with a genotype associated with slow caffeine metabolism or altered sensitivity to caffeine are at increased risk of MI associated with coffee consumption. Cases with a first non-fatal MI and population-based controls living in Costa Rica, matched for age, sex and area of residence were genotyped by RFLP-PCR. Caffeinated coffee consumption and smoking status was determined by questionnaire. Since CYP1A2 also activates mutagens that may lead to DNA damage contributing to heart disease, our initial study was to examine whether CYPIA2 genotype was associated with risk of MI. The low inducibility CYP1A2  genotype was associated with an increased risk of MI, regardless of smoking status, suggesting that a substrate of CYP1A2 that is detoxified rather than activated may play a role in heart disease. This led us to examine the role CYP1A2 may play in the association between coffee consumption and risk of MI. Coffee consumption was associated with an increased risk of MI only among those with the low inducibility CYP1A2 genotype, corresponding to slow caffeine metabolism, suggesting that caffeine plays a major role in this association. Although ADORA2A genotype did not modify the association between coffee consumption and risk of MI, individuals with the ADORA2A genotype associated with caffeine-induced anxiety were found to limit their caffeine intake. The results from this investigation suggest that genetic variation in caffeine metabolism modifies the risk of MI associated with coffee consumption, and genetic variation in caffeine sensitivity affects caffeine consumption behavior.
Notes: Source: Dissertation Abstracts International, Volume: 68-01, Section: B, page: 0217.

Thesis (Ph.D.)--University of Toronto, 2006.

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