Caffeine intake and CYP1A2 variants associated with high caffeine intake protect non-smokers from hypertension

Guessous, Idris; Dobrinas, Maria; Kutalik, Zoltán; Pruijm, Menno; Ehret, Georg Benedikt; Maillard, Marc Aimé Charles; Bergmann, Sven; Beckmann, Jacques S; Cusi, Daniele; Rizzi, Federica Rossana; Cappuccio, Franco; Cornuz, Jacques; Paccaud, Fred; Mooser, Vincent; Gaspoz, Jean-Michel; Waeber, Gérard; Burnier, Michel; Vollenweider, Peter; Eap, Chin Bin; Bochud, Murielle

doi:10.1093/hmg/dds137

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Title		Caffeine intake and CYP1A2 variants associated with high caffeine intake protect non-smokers from hypertension
Authors		Guessous, Idris Dobrinas, Maria Kutalik, Zoltán Pruijm, Menno Ehret, Georg Benedikt Maillard, Marc Aimé Charles Bergmann, Sven Beckmann, Jacques S Cusi, Daniele Rizzi, Federica Rossana Cappuccio, Franco Cornuz, Jacques Paccaud, Fred Mooser, Vincent Gaspoz, Jean-Michel Waeber, Gérard Burnier, Michel Vollenweider, Peter Eap, Chin Bin Bochud, Murielle show all authors [1 - 20]
Published in		Human Molecular Genetics. 2012, vol. 21, no. 14, p. 3283-3292
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.
Keywords		Adult — Aged — Blood Pressure — Caffeine/metabolism — Cytochrome P-450 CYP1A2/genetics/metabolism — European Continental Ancestry Group/genetics — Female — Genetic Variation — Genotype — Humans — Hypertension/genetics/metabolism/physiopathology/prevention & control — Male — Middle Aged — Polymorphism, Genetic — Smoking/genetics/metabolism/physiopathology
Identifiers		DOI: 10.1093/hmg/dds137 PMID: 22492992
Full text		Article (Published version) (172 Kb) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine clinique / Département de santé et médecine communautaires / Institut de médecine de premier recours
Research group		Groupe Jean-Michel Gaspoz (23)
Citation (ISO format)		GUESSOUS, Idris et al. Caffeine intake and CYP1A2 variants associated with high caffeine intake protect non-smokers from hypertension. In: Human Molecular Genetics, 2012, vol. 21, n° 14, p. 3283-3292. https://archive-ouverte.unige.ch/unige:31666