p450 - publications

Predict more p450 - ligand interactions now!

1. Hum Mol Genet. 2012 Apr 16. [Epub ahead of print]

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

Guessous I, Dobrinas M, Kutalik Z, Pruijm M, Ehret G, Maillard M, Bergmann S,
Beckmann JS, Cusi D, Rizzi F, Cappuccio F, Cornuz J, Paccaud F, Mooser V, Gaspoz
JM, Waeber G, Burnier M, Vollenweider P, Eap CB, Bochud M.

Community Prevention Unit, University Institute of Social and Preventive Medicine
(IUMSP), Lausanne University Hospital, Lausanne, Switzerland.

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.

PMID: 22492992 [PubMed - as supplied by publisher]