CYP1A2 and coffee intake and the modifying effect of sex, age, and smoking

CYP1A2 and coffee intake and the modifying effect of sex, age, and smoking
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DOI:
10.3945/ajcn.111.027102
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发表时间:
2012-07-01
影响因子:
7.1
通讯作者:
Visser, Loes E.
Visser, Loes E.
中科院分区:
医学1区
文献类型:
--
作者:
Rodenburg, Eline M.;Eijgelsheim, Mark;Visser, Loes E.

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背景:CYP1A2(细胞色素1A2)参与某些药物和咖啡因的代谢,其活性受性别、年龄、吸烟等因素的影响。单核苷酸多态(SNP)rs762551a和gt;C已被报道会改变酶活性。目的:目的:研究CYP1A2、性别、年龄和吸烟对咖啡摄入量的影响。设计:在鹿特丹的人群队列研究中,选择所有有全基因组关联数据的咖啡饮用者。因为SNP rs762551不在Illumina 550平台上,所以使用SNP rs2472299作为代理,rs762551的A等位基因与rs2472299的G等位基因连锁。使用线性回归分析来确定rs2472299、性别、年龄和吸烟对咖啡摄入量的影响和交互作用。使用多变量一般线性模型计算了不同吸烟和性别阶层的每个基因的咖啡摄入量的调整几何平均值。结果:rs2472299G>A、女性和不吸烟与咖啡摄入量显著负相关。携带rs2472299G>A纯合子的不吸烟女性咖啡摄入量最低(3.49杯/d,相当于436毫升)。所有因素对咖啡摄入量的贡献几乎是线性的,没有A等位基因的吸烟者咖啡摄入量最高(5.32杯/d;相当于665mL)。结论:rs2472299G>A与rs762551A>C连锁,性别、年龄和吸烟对咖啡摄入量有显著影响。AM J Clin Nutr 2012;96:182-7。
Background: The enzyme CYP1A2 (cytochrome 1A2) is involved in the metabolism of certain drugs and caffeine, and its activity can be influenced by factors such as sex, age, and smoking. The single nucleotide polymorphism (SNP) rs762551A>C, which has also been studied for its modifying effect on cardiovascular disease, has been reported to alter enzyme activity.Objective: The objective was to study the effect of CYP1A2, sex, age, and smoking on coffee intake.Design: Within the Rotterdam Study, a population-based cohort, all coffee drinkers for whom genome-wide association data were available were selected. Because SNP rs762551 was not on the Illumina 550 platform, SNP rs2472299 was used as a proxy, with the A allele of rs762551 linked to the G allele of rs2472299. Linear regression analyses were used to determine the effect and interaction of rs2472299, sex, age, and smoking on coffee intake. Adjusted geometric means of coffee intake were calculated per genotype for the different smoking and sex strata by using multivariable general linear models. A combined analysis, with the use of a "risk score," was performed to determine the contribution of each separate factor.Results: rs2472299G>A, female sex, and nonsmoking were significantly inversely related to coffee intake. Coffee intake was lowest in nonsmoking women homozygous for rs2472299G>A (3.49 cups/d; similar to 436 mL). All factors contributed almost linearly to the intake of coffee, with the highest coffee intake in smoking men without the A allele (5.32 cups/d; similar to 665 mL).Conclusion: rs2472299G>A, linked to rs762551A>C, sex, age, and smoking significantly contribute to coffee intake. Am J Clin Nutr 2012;96:182-7.