More on ADORA.
More on ADORA.
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更多关于阿多拉的信息。
DOI：
10.1007/s00213-010-2003-8
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发表时间：
2010
影响因子：
3.4
通讯作者：
deWit,Harriet
中科院分区：
文献类型：
--
作者：
Yang,Amy;Childs,Emma;Palmer,AbrahamA;deWit,Harriet
致《精神药理学》编辑的信：我们最近发表了一篇关于影响对咖啡因的反应和咖啡因摄入的遗传因素的综述（Yang et al. 2010）。不幸的是，我们的评论就在关于这个主题的另一篇重要论文发表之前出版（Rogers et al. 2010）。在这里，我们试图将罗杰斯等人的新发现与我们的审查结论相结合。最近发表的研究由罗杰斯等人。（2010）研究了与咖啡因诱导的焦虑相关的单核苷酸多态性（SNP）是否也可能影响咖啡因的习惯性摄入，以及习惯性摄入是否会调节咖啡因的致焦虑作用。该实验研究了两种腺苷受体（ADORA 2A和ADORA 1）中的SNP与非消费者/轻度消费者和中度/重度消费者咖啡因引起的焦虑之间的关联。与之前的报道（Alfred et al. 2003;查尔兹et al. 2008）一致，研究人员发现rs 5751876的T/T基因型（p= 0.002）与咖啡因诱导的焦虑之间存在关联。对于rs3761422（p= 0.004）发现了类似的结果，其与rs 5751876处于强连锁不平衡。在检测的8个ADORA 2A基因座（α=0.00625，经多重检验调整）或7个ADORA 1基因座（α= 0.00714）中，与其他SNP无关联。然而，这种影响被习惯性消费所缓和。所有非消费者/轻消费者表现出显着增加后，咖啡因的焦虑，而中/重消费者没有，无论基因型。与他们的假设相反，不同基因型之间的咖啡因总摄入量没有差异。因此，虽然rs 5751876与咖啡因后的焦虑有关，但这种影响可能会被习惯性消费所缓和，从而使普通消费者对咖啡因的致焦虑作用产生耐受性。作者得出结论，对咖啡因引起的焦虑的易感性似乎不会影响习惯性咖啡因摄入的水平。这些发现证实了以前的一些发现（查尔兹等人，2008年，Alfred等人，2003年），但与另一项研究（Cornelis等人，2007年）不一致。rs 5751876 T/T基因型与咖啡因诱导的焦虑之间的关联与查尔兹等人的报告一致。（2008）和Alfred et al.（2003）;然而，这种基因型和咖啡因摄入量之间缺乏关联与Cornelis et al.（2007），他们发现rs 5751876 T/T个体，特别是吸烟者，消耗较少的咖啡因。这两项研究在非常不同的人群中进行：罗杰斯研究招募了平均年龄为30-35岁的健康高加索欧洲人，而科内利斯研究测试了平均年龄为56-57岁的哥斯达黎加心肌梗死幸存者。因此，年龄和生存差异等其他因素可能有助于观察到ADORA 2A基因型对咖啡因摄入量的影响。研究发现，经常消费咖啡因的人比轻度消费者报告的焦虑少，无论基因型如何，可以用几个因素来解释。首先，在大量的咖啡因消费者中，急性剂量的药物的潜在致焦虑作用可能被咖啡因的存在和缓解所掩盖
Letter to the editors of Psychopharmacology: We recently published a review on genetic factors influencing responses to caffeine and consumption of caffeine (Yang et al. 2010). Unfortunately, our review went to press just before an important additional paper was published on this topic (Rogers et al. 2010). Here, we attempt to integrate the new findings from Rogers et al. with the conclusions of our review. The recently published study by Rogers et al.(2010) investigated whether single nucleotide polymorphisms (SNPs) associated with caffeine-induced anxiety might also affect habitual caffeine intake and whether habitual intake moderates the anxiogenic effect of caffeine. The experiment examined associations between SNPs in two adenosine receptors (ADORA2A and ADORA1) and caffeine-induced anxiety in non-consumers/light consumers and medium/heavy consumers of caffeine. Consistent with previous reports (Alsene et al. 2003; Childs et al. 2008), the researchers found an association between the T/T genotype of rs5751876 (p= 0.002) and caffeine-induced anxiety. Similar results were found for rs3761422 (p= 0.004), which is in strong linkage disequilibrium with rs5751876. There were no associations with other SNPs in the eight ADORA2A loci (α=0.00625, adjusted for multiple testing) or the seven ADORA1 loci (α= 0.00714) tested. However, this effect was moderated by habitual consumption. All non-consumers/light consumers exhibited significant increases in anxiety after caffeine while medium/heavy consumers did not, regardless of genotype. Contrary to their hypothesis, total caffeine consumption did not differ among different genotypes. Thus, it appears that while rs5751876 is associated with anxiety after caffeine, this effect may be moderated by habitual consumption such that regular consumers develop tolerance to the anxiogenic effects of caffeine. The authors conclude that susceptibility to caffeine-induced anxiety does not appear to influence levels of habitual caffeine intake.These findings corroborate some previous findings (Childs et al. 2008, Alsene et al. 2003), but are inconsistent with another study (Cornelis et al. 2007). The association between rs5751876 T/T genotype and caffeine-induced anxiety is consistent with reports by Childs et al.(2008) and Alsene et al.(2003); however, the lack of association between this genotype and caffeine consumption is not consistent with findings reported by Cornelis et al.(2007), who found that rs5751876 T/T individuals, particularly smokers, consumed less caffeine. The two studies were conducted in very different populations: the Rogers study recruited healthy Caucasian Europeans with mean age of 30–35 years, whereas the Cornelis study tested Costa Rican survivors of myocardial infarction with mean age of 56–57 years. Therefore, other factors such as age and survival differences may have contributed to the observed effects of ADORA2A genotype on caffeine consumption. The finding that frequent consumers of caffeine report less anxiety than lighter consumer, regardless of genotype, can be explained by several factors. First, in heavy caffeine consumers, the potential anxiogenic effects of acute doses of the drug may be masked by presence of, and relief from, caffeine