一氧化氮合酶3（NOS3）基因多态性对偏头痛发作中三环类抗抑郁药反应的影响。
Effect of NOS3 gene polymorphism on response to Tricyclic antidepressants in migraine attacks.
作者信息
Molana Aliasghar, Mehrpour Masoud, Vousooghi Nasim, Hajighasem Mahmoud Reza, Joghataei Mohammad Taghi
机构信息
Department of Neuroscience, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Neurology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran.
出版信息
Iran J Neurol. 2014 Jul 4;13(3):154-9.
BACKGROUND
Migraine is a chronic neurological disorder, characterized by recurrent moderate to severe headaches. Worldwide migraine affects nearly 15%. Studies suggest that genes involved in the production of nitric oxide (NO) may act as genetic factors for migraine. NO synthase 3 (NOS3) by expressing enzyme NOS regulates endothelial derived NO. One class of medications used as first-line treatment in migraine prophylaxis is tricyclic antidepressants (TCAs). The aim of this study was to determine effects of NOS3 gene Glu298Asp polymorphism in the production of NO and response of patients to TCAs in migraine attacks.
METHODS
A total of 80 migraine patients were invited to participate in the study. Patients recorded the characteristics of their migraine attacks such as frequency of attacks and intensity of headaches for the 1(st) month of the study. Then peripheral blood samples were taken from all subjects in order to determine patients' genotype distribution, mRNA expression level of NOS3 and NO content of plasma. Patients were then instructed to use 25 mg nortriptyline at night before bed for 3 months. At the end of 3(rd) month of the treatment patients again recorded the migraine characteristics for 1 month and blood sampling was performed in order to determine the level of plasma NO.
RESULTS
The patients' genotype distribution for TT, GT, and GG was 9, 24, and 47 subjects, respectively. Mean NO level in patients with TT genotype was less in comparison to GT and GG genotypes before and after use of TCAs (P < 0.05). Mean intensity of headaches in patients with TT genotype was lower in comparison to GT and GG genotypes before and after use of TCAs (based on verbal numerical rating scale). Mean frequency of migraine attacks after use of TCAs was significantly decreased in all genotypes of NOS3 Glu298Asp polymorphism particularly in TT genotype (P < 0.05).
CONCLUSION
Presence of T allele of the Glu298Asp polymorphism may be a factor for TT genotype patients to produce less NO and is a favorable factor for better response to TCAs in reducing migraine attacks in comparison to GT and GG genotypes.
背景
偏头痛是一种慢性神经疾病，其特征为反复发作的中度至重度头痛。全球范围内，偏头痛的患病率接近15%。研究表明，参与一氧化氮（NO）生成的基因可能是偏头痛的遗传因素。一氧化氮合酶3（NOS3）通过表达一氧化氮合酶来调节内皮源性一氧化氮。在偏头痛预防性治疗中用作一线治疗的一类药物是三环类抗抑郁药（TCA）。本研究的目的是确定NOS3基因Glu298Asp多态性对NO生成的影响以及偏头痛发作患者对TCA的反应。
方法
共邀请80名偏头痛患者参与本研究。患者记录了研究第1个月偏头痛发作的特征，如发作频率和头痛强度。然后采集所有受试者的外周血样本，以确定患者的基因型分布、NOS3的mRNA表达水平和血浆NO含量。随后指导患者在睡前服用25毫克去甲替林，持续3个月。在治疗的第3个月末，患者再次记录1个月的偏头痛特征，并进行采血以测定血浆NO水平。
结果
TT、GT和GG基因型的患者分别有9例、24例和47例。在使用TCA前后，TT基因型患者的平均NO水平低于GT和GG基因型患者（P < 0.05）。根据言语数字评定量表，在使用TCA前后，TT基因型患者的平均头痛强度低于GT和GG基因型患者。在NOS3 Glu298Asp多态性的所有基因型中，尤其是TT基因型，使用TCA后偏头痛发作的平均频率显著降低（P < 0.05）。
结论
Glu298Asp多态性的T等位基因的存在可能是TT基因型患者产生较少NO的一个因素，与GT和GG基因型相比，它是对TCA在减少偏头痛发作方面有更好反应的一个有利因素。
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