title: CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension.
abstract: 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.
authors.affiliation: Clinica Medica 4, University of Padova, via Giustiniani, 2- 35128 Padova, Italy. palatini@unipd.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Palatini
authors.forename: Giulio
authors.initials: G
authors.lastname: Ceolotto
authors.forename: Fabio
authors.initials: F
authors.lastname: Ragazzo
authors.forename: Francesca
authors.initials: F
authors.lastname: Dorigatti
authors.forename: Francesca
authors.initials: F
authors.lastname: Saladini
authors.forename: Italia
authors.initials: I
authors.lastname: Papparella
authors.forename: Lucio
authors.initials: L
authors.lastname: Mos
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zanata
authors.forename: Massimo
authors.initials: M
authors.lastname: Santonastaso
mesh_terms: 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
chemical_list: D003069:Coffee; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D004837:Epinephrine