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Caffeine intake, and CYP1A2 variants associated with high caffeine intake, protect non-smokers from hypertension.
MedLine Citation:
PMID:  22492992     Owner:  NLM     Status:  Publisher    
The 15q24.1 locus, including CYP1A2, is associated with blood pressure. 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 blood pressure, 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: blood pressure, 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 blood pressure after quitting smoking (p=0.049 and p=0.02 for systolic and diastolic blood pressure, 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 blood pressure (p=0.01). In Mendelian randomization analyses using rs1133323 as instrument, each cup of caffeinated beverage was negatively associated with systolic blood pressure (-9.57 [-16.22, -2.91] mm Hg). The associations of CYP1A2 variants with blood pressure were modified by reported caffeine intake. These observational and quasi-experimental results strongly support a causal role of CYP1A2 in blood pressure control via caffeine intake.
Idris Guessous; Maria Dobrinas; Zoltan 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; Murielle Bochud
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-5
Journal Detail:
Title:  Human molecular genetics     Volume:  -     ISSN:  1460-2083     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Community Prevention Unit, University Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland.
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