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

Article Article scientifique Article Caffeine intake and CYP1A2 variants associated with high caffeine intake protect non-smokers from hypertension eng 2012 author Guessous Idris 760565 author Dobrinas Maria 640060 author Kutalik Zoltán author Pruijm Menno 641036 author Ehret Georg Benedikt 98462 author Maillard Marc Aimé Charles 54695 author Bergmann Sven author Beckmann Jacques S author Cusi Daniele author Rizzi Federica Rossana 100442 author Cappuccio Franco author Cornuz Jacques 862130 author Paccaud Fred author Mooser Vincent author Gaspoz Jean-Michel 126367 author Waeber Gérard author Burnier Michel author Vollenweider Peter 724488 author Eap Chin Bin 648560 author Bochud Murielle 41043 3283-3292 10.1093/hmg/dds137 22492992 0964-6906 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. 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 Dewey 613 Dewey 615 Dewey 616 31 Section des sciences pharmaceutiques 17 56 Département de médecine 221 201 Institut de médecine de premier recours 22A9 false 16 Groupe Jean-Michel Gaspoz 23 Human molecular genetics 21 14 24176626-fd40-4e59-a99b-d4955318e342 Article (Published version) Restricted Caffeine intake and CYP1A2.pdf 176200 application/pdf restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département de santé et médecine communautaires / Institut de médecine de premier recours

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Caffeine intake and CYP1A2 variants associated with high caffeine intake protect non-smokers from hypertension	Human molecular genetics			2012	856	2

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