Community Prevention Unit, University Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland.
Hum Mol Genet. 2012 Jul 15;21(14):3283-92. doi: 10.1093/hmg/dds137. Epub 2012 Apr 5.
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.
15q24.1 基因座，包括 CYP1A2，与血压（BP）有关。CYP1A2 rs762551 C 等位基因与 CYP1A2 酶活性降低有关。CYP1A2 代谢咖啡因，并受吸烟诱导。咖啡因摄入与高血压之间的关联仍存在争议。我们探讨了 CYP1A2 变体和 CYP1A2 酶活性对 BP 的影响，重点关注咖啡因作为 CYP1A2 效应的潜在介导物。进行了四项观察性（n = 16719）和一项准实验性研究（n = 106），其中包括欧洲成年人。结果测量指标为 BP、咖啡因摄入量、CYP1A2 活性以及 rs762551、rs1133323 和 rs1378942 多态性。CYP1A2 变体与非吸烟者的高血压有关，但与吸烟者无关（CYP1A2-吸烟相互作用 P = 0.01）。rs762551 CC、CA 和 AA 基因型的高血压比值比（95%CI）分别为 1（参考）、0.78（0.59-1.02）和 0.66（0.50-0.86），P = 0.004。其他变体的结果相似。戒烟后，CYP1A2 活性与 BP 呈线性负相关（收缩压和舒张压分别为 P = 0.049 和 P = 0.02），但吸烟时无此关联。在非吸烟者中，CYP1A2 变体与报告的咖啡因摄入量较高有关，而后者又与高血压和 BP 较低的几率较低有关（P = 0.01）。在使用 rs1133323 作为工具的孟德尔随机化分析中，每杯含咖啡因的饮料与收缩压呈负相关[-9.57（-16.22，-2.91）mmHg]。CYP1A2 变体与 BP 的关联受报告的咖啡因摄入量的影响。这些观察性和准实验性结果强烈支持 CYP1A2 通过咖啡因摄入对 BP 控制的因果作用。
