Journal Article

Caffeine intake and <i>CYP1A2</i> variants associated with high caffeine intake protect non-smokers from hypertension

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

in Human Molecular Genetics

Volume 21, issue 14, pages 3283-3292
Published in print July 2012 | ISSN: 0964-6906
Published online April 2012 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/dds137
Caffeine intake and CYP1A2 variants associated with high caffeine intake protect non-smokers from hypertension

Show Summary Details

Preview

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.

Journal Article.  6179 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.