Association of RAMP1 rs7590387 with the risk of migraine transformation into medication overuse headache

Abstract

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.

Methods: 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.

Results: 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).

Conclusion: These results suggest that RAMP1 rs7590387 may have a role in the transformation of episodic migraine into MOH.

Keywords: CGRP-related gene; medication overuse headache; migraine; polymorphism; susceptibility; triptan.