Cross-sectional Assessment of the Consequences of a GTP Cyclohydrolase 1 Haplotype for Specialized Tertiary Outpatient Pain Care
Cross-sectional Assessment of the Consequences of a GTP Cyclohydrolase 1 Haplotype for Specialized Tertiary Outpatient Pain Care
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DOI：
10.1097/ajp.0b013e3181b43e12
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发表时间：
2009-11-01
影响因子：
2.9
通讯作者：
Loetsch, Joern
中科院分区：
文献类型：
--
作者：
Doehring, Alexandra;Freynhagen, Rainer;Loetsch, Joern
目的：三磷酸鸟苷环化水解酶基因（GCH 1）的功能降低变体与明确定义的患者和健康志愿者队列中的疼痛减轻有关。我们解决了这个问题，这种遗传关联是否发挥作用，在门诊pain therapy.Methods：在一项横断面观察性研究，523例患者参加了3个不同的三级保健门诊疼痛中心在德国大学医院。在519名白人患者中，可以分析424名患者的数据，以确定以前称为“疼痛保护”的GCH 1单倍型与疼痛治疗的关键特征（1）实际疼痛，（2）阿片类药物剂量和（3）疼痛治疗持续时间的功能关联。结果：等位基因频率为14.2%，疼痛保护单倍型在疼痛患者中并不比普通人群中更罕见（P = 0.344）。然而，在所有3个治疗参数中观察到GCH 1单倍型的基因剂量依赖性效应的趋势。单倍型携带者倾向于具有较低的实际24分（n = 424; P = 0.18），需要较低的阿片类药物小时疼痛剂量（P = 0.096），并且在专门的疼痛治疗中显着缩短（P = 0.004）。后者主要适用于纯合子携带者和杂合子（的。校正t检验：P = 0.06）或非载体（P = 0.011）的haplotype.Conclusions：结果加强了支持一个温和的，但可重复的和一致的疼痛保护作用与GCH 1单倍型已知减少GCH 1，从而BH 4上调。在独立验证之前，结果可能指向GCH 1上调减少延迟疼痛治疗需要的预防作用。
Objectives: Reduced-function variants of the guanosine triphosphate cyclohydrolase gene (GCH1) have been associated with reduced pain in well-defined cohorts of patients and healthy volunteers. We addressed the question whether this genetic association plays a role in outpatient pain therapy.Methods: In a cross-sectional observational study, 523 patients were enrolled in 3 different tertiary care outpatient pain centers at German University hospitals. Of the 519 Caucasian patients, data from 424 could be analyzed for functional associations of the formerly named "pain-protective" GCH1 haplotype with the key characteristics of pain therapy being (1) actual pain, (2) opioid dosing, and (3) pain therapy duration.Results: With an allelic frequency of 14.2% the pain-protective haplotype was not rarer among pain patients than in the general population (P = 0.344). However, a tendency toward gene dose-dependent effects of the GCH1 haplotype was observed in all the 3 therapy parameters. Carriers of the haplotype tended to have lower actual 24 scores (n = 424; P = 0.18), require lower opioid-hour pain doses (P = 0.096), and were significantly shorter on specialized pain therapy (P = 0.004). The latter applied predominantly to differences between homozygous carriers and heterozygous (of.-corrected t test: P = 0.06) or non-carriers (P = 0.011) of the haplotype.Conclusions: The results strength the support for a modest yet reproducible and consistent pain-protective effect associated with a GCH1 haplotype known to reduce GCH1 and thus BH4 up-regulation. Pending independent verification, the results might point to a prophylactic role of decreased GCH1 up-regulation delaying the need for pain therapy.