Department of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara, Italy.
Headache Science Centre, National Neurological Institute C. Mondino, Pavia, Italy.
Headache. 2015 May;55(5):658-68. doi: 10.1111/head.12559. Epub 2015 Apr 17.
OBJECTIVES/BACKGROUND: We herein investigated the role of polymorphisms in calcitonin gene-related peptide (CGRP)-related genes looking at the association of rs3781719 (T > C) in the calcitonin gene-related polypeptide-alpha (CALCA) gene and of rs3754701 (T > A) and rs7590387 (C > G) at the receptor activity modifying 1 (RAMP1) locus with triptan response in patients with migraine without aura (MwoA). In addition, their role was evaluated as risk factors for transformation of episodic migraine into medication overuse headache (MOH). The CGRP has a central role in the pathogenesis of migraine; however, little information is currently available concerning the role of polymorphisms in CGRP-related genes as determinants of clinical response to anti-migraine drugs or as risk factors for migraine chronification.
Genotyping was conducted retrospectively by real-time polymerase chain reaction allelic discrimination assay in 219 patients with MwoA and 130 with MOH in whom migraine was the primary headache type. Gene variants association was evaluated by logistic regression analysis adjusted by confounding factors. The threshold of statistical significance was set according to the total number of polymorphisms analyzed in the current study and in previous publications arising from overlapping datasets.
No evidence of association was found between the three polymorphisms tested and triptan response in MwoA patients. Conversely, carriers of RAMP1 rs7590387GG displayed a lower risk of episodic migraine transformation into MOH (vs C allele carriers, odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.13-0.57, P = 0.0002; threshold of significance set at P < 0.0029). When genotype distribution for RAMP1 rs7590387 was compared between healthy controls (n = 209) and MOH patients, carriers of rs7590387GG were found at lower risk of developing MOH (OR: 0.43, 95%CI: 0.22-0.85, P = 0.011).
These results suggest that RAMP1 rs7590387 may have a role in the transformation of episodic migraine into MOH.
目的/背景：我们在此研究降钙素基因相关肽（CGRP）相关基因中的多态性的作用，观察降钙素基因相关肽-α（CALCA）基因中 rs3781719（T>C）和受体活性修饰蛋白 1（RAMP1）基因中 rs3754701（T>A）和 rs7590387（C>G）多态性与无先兆偏头痛（MwoA）患者曲普坦反应之间的关联。此外，还评估了它们作为发作性偏头痛转化为药物过度使用性头痛（MOH）的风险因素的作用。CGRP 在偏头痛的发病机制中起核心作用；然而，目前关于 CGRP 相关基因多态性作为抗偏头痛药物临床反应的决定因素或偏头痛慢性化的风险因素的信息有限。
通过实时聚合酶链反应等位基因鉴别分析对 219 例 MwoA 患者和 130 例 MOH 患者进行了回顾性基因分型，其中偏头痛是原发性头痛类型。通过逻辑回归分析调整混杂因素评估基因变异与关联。根据当前研究中和来自重叠数据集的先前出版物中分析的总多态性数设置统计显着性阈值。
未发现测试的三种多态性与 MwoA 患者的曲普坦反应之间存在关联。相反，RAMP1 rs7590387GG 携带者发作性偏头痛转化为 MOH 的风险较低（与 C 等位基因携带者相比，比值比 [OR]：0.27，95%置信区间 [CI]：0.13-0.57，P=0.0002；显着性阈值设定为 P<0.0029）。当 RAMP1 rs7590387 基因型分布在健康对照（n=209）和 MOH 患者之间进行比较时，发现 rs7590387GG 携带者发生 MOH 的风险较低（OR：0.43，95%CI：0.22-0.85，P=0.011）。
这些结果表明，RAMP1 rs7590387 可能在发作性偏头痛转化为 MOH 中起作用。
