CYP1A2 and coffee intake and the modifying effect of sex, age, and smoking.
BACKGROUND
The enzyme CYP1A2 (cytochrome 1A2) is involved in the metabolism of certain drugs and caffeine, and its activity can be influenced by factors such as sex, age, and smoking. The single nucleotide polymorphism (SNP) rs762551A>C, which has also been studied for its modifying effect on cardiovascular disease, has been reported to alter enzyme activity.


OBJECTIVE
The objective was to study the effect of CYP1A2, sex, age, and smoking on coffee intake.


METHODS
Within the Rotterdam Study, a population-based cohort, all coffee drinkers for whom genome-wide association data were available were selected. Because SNP rs762551 was not on the Illumina 550 platform, SNP rs2472299 was used as a proxy, with the A allele of rs762551 linked to the G allele of rs2472299. Linear regression analyses were used to determine the effect and interaction of rs2472299, sex, age, and smoking on coffee intake. Adjusted geometric means of coffee intake were calculated per genotype for the different smoking and sex strata by using multivariable general linear models. A combined analysis, with the use of a "risk score," was performed to determine the contribution of each separate factor.


RESULTS
rs2472299G>A, female sex, and nonsmoking were significantly inversely related to coffee intake. Coffee intake was lowest in nonsmoking women homozygous for rs2472299G>A (3.49 cups/d; ∼436 mL). All factors contributed almost linearly to the intake of coffee, with the highest coffee intake in smoking men without the A allele (5.32 cups/d; ∼665 mL).


CONCLUSIONS
rs2472299G>A, linked to rs762551A>C, sex, age, and smoking significantly contribute to coffee intake.
Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands. e.rodenburg@erasmusmc.nl
Eline M
EM
Rodenburg
Mark
M
Eijgelsheim
Johanna M
JM
Geleijnse
Najaf
N
Amin
Cornelia M
CM
van Duijn
Albert
A
Hofman
Andre G
AG
Uitterlinden
Bruno H
BH
Stricker
Loes E
LE
Visser
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D003069:Coffee; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012727:Sex Characteristics; D012907:Smoking / Q000378:metabolism*
D003069:Coffee; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2