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CALCA 和 TRPV1 基因多态性与接受肉毒毒素 A 治疗的女性慢性偏头痛患者的良好预后相关。

CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA.

机构信息

Clinical Analysis Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.

Headache Unit, Neurology Department, Hospital Clínico Universitario de Valladolid, Avda. Ramón y Cajal 3, 47005, Valladolid, Spain.

出版信息

J Headache Pain. 2019 Apr 23;20(1):39. doi: 10.1186/s10194-019-0989-9.

Abstract

BACKGROUND

Some variables have been proposed as predictors of efficacy of OnabotulinumtoxinA in chronic migraine patients, but data available are inconclusive. We aimed to analyse the influence of single nucleotide polymorphisms in the response to OnabotulinumtoxinA.

METHODS

We included 156 female patients treated with OnabotulinumtoxinA accordingly to PREEMPT paradigm in three headache units. OnabotulinumtoxinA was offered to patients that had not responded to topiramate and at least one other preventative. Age at first procedure was 43.7 ± 11.8 years (16-74). Patients with a reduction of at least 50% in the number of migraine days after two OnabotulinumtoxinA procedures were considered as responders. We analysed 25 polymorphisms selected for their relevance regarding migraine pathophysiology and their association with migraine according to previously published genome-wide association studies. Genotyping was performed using KASP probes and a LightCycler-480 (Roche-Diagnostics). Allelic, genotypic frequencies and dominance/recesivity hypothesis of the allelic variants were compared between responders and non-responders by Fisher's exact test.

RESULTS

Response to treatment with OnabotulinumtoxinA was achieved in 120 patients (76,9%). Two polymorphisms showed differences: CALCA rs3781719, where allele C represents 26.9% in responders and 40.9% in non-responders (p = 0.007, OR = 3.11 (1.33-7.26)); and TRPV1 rs222749, where allele A represents 4.17% in responders and 12.5% in non-responders (p = 0.013, OR = 3.29 (1.28-8.43)). No significant differences in rest of polymorphisms or clinical or demographic variables were found.

CONCLUSIONS

Polymorphic variations of CALCA and TRPV1 genes might play a role as prognostic markers of efficacy of OnabotulinumtoxinA in chronic migraine female patients in our population.

摘要

背景

一些变量被提出作为预测慢性偏头痛患者接受肉毒毒素治疗效果的指标,但目前的数据尚无定论。我们旨在分析单核苷酸多态性对肉毒毒素反应的影响。

方法

我们纳入了三个头痛单位中按照 PREEMPT 方案接受肉毒毒素治疗的 156 名女性患者。肉毒毒素治疗方案用于那些对托吡酯和至少一种其他预防性药物治疗无反应的患者。首次治疗时的年龄为 43.7±11.8 岁(16-74 岁)。在接受两次肉毒毒素治疗后,偏头痛天数减少至少 50%的患者被认为是有反应者。我们分析了 25 种单核苷酸多态性,这些多态性选择的依据是它们与偏头痛病理生理学的相关性及其根据先前发表的全基因组关联研究与偏头痛的相关性。使用 KASP 探针和 LightCycler-480(罗氏诊断)进行基因分型。通过 Fisher 精确检验比较反应者和无反应者之间等位基因、基因型频率以及等位基因变异的显性/隐性假说。

结果

120 名患者(76.9%)对肉毒毒素治疗有反应。两种多态性存在差异:CALCA rs3781719 中,等位基因 C 在有反应者中占 26.9%,在无反应者中占 40.9%(p=0.007,OR=3.11(1.33-7.26));TRPV1 rs222749 中,等位基因 A 在有反应者中占 4.17%,在无反应者中占 12.5%(p=0.013,OR=3.29(1.28-8.43))。在其余的多态性或临床或人口统计学变量中未发现显著差异。

结论

在我们的人群中,CALCA 和 TRPV1 基因的多态性变异可能作为慢性偏头痛女性患者接受肉毒毒素治疗效果的预后标志物。

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