title: Caffeine intake and CYP1A2 variants associated with high caffeine intake protect non-smokers from hypertension.
abstract: The 15q24.1 locus, including CYP1A2, is associated with blood pressure (BP). The CYP1A2 rs762551 C allele is associated with lower CYP1A2 enzyme activity. CYP1A2 metabolizes caffeine and is induced by smoking. The association of caffeine consumption with hypertension remains controversial. We explored the effects of CYP1A2 variants and CYP1A2 enzyme activity on BP, focusing on caffeine as the potential mediator of CYP1A2 effects. Four observational (n = 16 719) and one quasi-experimental studies (n = 106) including European adults were conducted. Outcome measures were BP, caffeine intake, CYP1A2 activity and polymorphisms rs762551, rs1133323 and rs1378942. CYP1A2 variants were associated with hypertension in non-smokers, but not in smokers (CYP1A2-smoking interaction P = 0.01). Odds ratios (95% CIs) for hypertension for rs762551 CC, CA and AA genotypes were 1 (reference), 0.78 (0.59-1.02) and 0.66 (0.50-0.86), respectively, P = 0.004. Results were similar for the other variants. Higher CYP1A2 activity was linearly associated with lower BP after quitting smoking (P = 0.049 and P = 0.02 for systolic and diastolic BP, respectively), but not while smoking. In non-smokers, the CYP1A2 variants were associated with higher reported caffeine intake, which in turn was associated with lower odds of hypertension and lower BP (P = 0.01). In Mendelian randomization analyses using rs1133323 as instrument, each cup of caffeinated beverage was negatively associated with systolic BP [-9.57 (-16.22, -2.91) mmHg]. The associations of CYP1A2 variants with BP were modified by reported caffeine intake. These observational and quasi-experimental results strongly support a causal role of CYP1A2 in BP control via caffeine intake.
authors.affiliation: Community Prevention Unit, University Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Idris
authors.initials: I
authors.lastname: Guessous
authors.forename: Maria
authors.initials: M
authors.lastname: Dobrinas
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kutalik
authors.forename: Menno
authors.initials: M
authors.lastname: Pruijm
authors.forename: Georg
authors.initials: G
authors.lastname: Ehret
authors.forename: Marc
authors.initials: M
authors.lastname: Maillard
authors.forename: Sven
authors.initials: S
authors.lastname: Bergmann
authors.forename: Jacques S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: Daniele
authors.initials: D
authors.lastname: Cusi
authors.forename: Federica
authors.initials: F
authors.lastname: Rizzi
authors.forename: Franco
authors.initials: F
authors.lastname: Cappuccio
authors.forename: Jacques
authors.initials: J
authors.lastname: Cornuz
authors.forename: Fred
authors.initials: F
authors.lastname: Paccaud
authors.forename: Vincent
authors.initials: V
authors.lastname: Mooser
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Gaspoz
authors.forename: Gérard
authors.initials: G
authors.lastname: Waeber
authors.forename: Michel
authors.initials: M
authors.lastname: Burnier
authors.forename: Peter
authors.initials: P
authors.lastname: Vollenweider
authors.forename: Chin B
authors.initials: CB
authors.lastname: Eap
authors.forename: Murielle
authors.initials: M
authors.lastname: Bochud
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure; D002110:Caffeine / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012907:Smoking / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D044465:White People / Q000235:genetics
chemical_list: D002110:Caffeine; D019388:Cytochrome P-450 CYP1A2