CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension.
OBJECTIVE
The longitudinal relationship between coffee use and hypertension is still controversial. Cytochrome P450 1A2 (CYP1A2) is the main responsible enzyme for the metabolism of caffeine. The aim of the present study was to investigate the effect of coffee intake on the risk of developing hypertension needing antihypertensive treatment in individuals stratified by CYP1A2 genotype.


METHODS
We assessed prospectively 553 young White individuals screened for stage 1 hypertension. Coffee intake was ascertained from regularly administered questionnaires. Incident physician-diagnosed hypertension was the outcome measure. Genotyping of CYP1A2 SNP was performed by real time PCR.


RESULTS
During a median follow-up of 8.2 years, 323 individuals developed hypertension. For carriers of the slow *1F allele (59%), hazard ratios of hypertension from multivariable Cox analysis were 1.00 in abstainers (reference), 1.72 (95%CI, 1.21-2.44) in moderate coffee drinkers (P = 0.03), and 3.00 (1.53-5.90) in heavy drinkers (P = 0.001). In contrast, hazard ratios for coffee drinkers with the rapid *1A/*1A genotype were 0.80 (0.52-1.23, P = 0.29) for moderate drinkers and 0.36 (0.14-0.89, P = 0.026) for heavy drinkers. In a two-way ANCOVA, a gene x coffee interactive effect was found on follow-up changes in systolic (P = 0.000) and diastolic (P = 0.007) blood pressure. Urinary epinephrine was higher in coffee drinkers than abstainers but only among individuals with slow *1F allele (P = 0.001).


CONCLUSIONS
These data show that the risk of hypertension associated with coffee intake varies according to CYP1A2 genotype. Carriers of slow *1F allele are at increased risk and should thus abstain from coffee, whereas individuals with *1A/*1A genotype can safely drink coffee.
Palatini
Paolo
P
Clinica Medica 4, University of Padova, via Giustiniani, 2- 35128 Padova, Italy. palatini@unipd.it
Ceolotto
Giulio
G
Ragazzo
Fabio
F
Dorigatti
Francesca
F
Saladini
Francesca
F
Papparella
Italia
I
Mos
Lucio
L
Zanata
Giuseppe
G
Santonastaso
Massimo
M
D000293:Adolescent; D000328:Adult; D003069:Coffee / Q000009:adverse effects*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D004837:Epinephrine / Q000652:urine; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012306:Risk
D003069:Coffee; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D004837:Epinephrine