Increased risk of hospitalization for ultrarapid metabolizers of cytochrome P450 2D6
Increased risk of hospitalization for ultrarapid metabolizers of cytochrome P450 2D6
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DOI：
10.2147/pgpm.s114211
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发表时间：
2017-01-01
影响因子：
1.9
通讯作者：
Bielinski, Suzette J.
中科院分区：
文献类型：
--
作者：
Takahashi, Paul Y.;Ryu, Euijung;Bielinski, Suzette J.
背景资料：细胞色素P450 2D 6（CYP 2D 6）负责临床使用的药物和其他环境暴露的代谢，但目前尚不清楚CYP 2D 6表型是否与不良健康结果相关。目的是确定与住院或急诊科（艾德）访问一组初级保健patients.Methods：在这项研究中，929名成年患者进行CYP 2D 6检测的风险CYP 2D 6表型的关联。主要结局是2005年1月至2014年9月住院或艾德访视的风险。将CYP 2D 6基因型解释为7种临床表型之一，从超快代谢型到慢代谢型，并将具有快代谢型表型的患者用作参考组。通过使用考克斯比例风险模型并调整年龄和性别，估计风险比（HR）和95%置信区间（CI），以发现CYP 2D 6表型与住院或艾德访视风险的相关性。（四分位距，46-52岁）; 74%的患者有3种或更少的慢性疾病，285例至少住院1次，496例至少有1次艾德访视。超快代谢型患者的住院风险高于快代谢型患者（47% vs 30%; HR，1.69; 95% CI，1.11-2.57），艾德访视的风险也是如此（62% vs 49%; HR，1.50; 95% CI，1.05-2.14）。对于慢代谢者和快代谢者，住院风险没有差异（HR，0.95; 95% CI，0.58-1.56），但艾德访视的风险增加（HR，1.38; 95% CI，0.96-1.98）结论：我们发现与CYP 2D 6快代谢者相比，超速代谢者住院或艾德访视的风险增加。进一步的研究确定的相关机制和最终的临床效用是必要的。
Background: Cytochrome P450 2D6 (CYP2D6) is responsible for the metabolism of clinically used drugs and other environmental exposures, but it is unclear whether the CYP2D6 phenotype is associated with adverse health outcomes. The aim was to determine the association of CYP2D6 phenotype with the risk of hospitalization or an emergency department (ED) visit among a group of primary care patients.Methods: In this study, 929 adult patients underwent CYP2D6 testing. The primary outcome was risk of hospitalization or an ED visit from January 2005 through September 2014. CYP2D6 genotypes were interpreted as 1 of 7 clinical phenotypes, from ultrarapid to poor metabolizer, and patients with the extensive metabolizer phenotype were used as the reference group. The hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for finding the association of CYP2D6 phenotypes with the risk of hospitalization or an ED visit by using Cox proportional hazard models and adjusting for age and sex.Results: The median age was 49 years (interquartile range, 46-52 years); 74% of patients had 3 or fewer chronic conditions, 285 had at least 1 hospitalization, and 496 had at least 1 ED visit. The risk of hospitalization was higher among patients who were ultrarapid metabolizers compared to extensive metabolizers (47% vs 30%; HR, 1.69; 95% CI, 1.11-2.57), as was the risk of an ED visit (62% vs 49%; HR, 1.50; 95% CI, 1.05-2.14). For poor metabolizers compared to extensive metabolizers, there was no difference in the risk of hospitalization (HR, 0.95; 95% CI, 0.58-1.56), but there was an increase in the risk of an ED visit (HR, 1.38; 95% CI, 0.96-1.98) (the difference was not statistically significant).Conclusion: We found an increased risk of hospitalization or an ED visit among ultrarapid compared to extensive CYP2D6 metabolizers. Further research identifying the mechanisms of the association and ultimate clinical utility is warranted.