CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA
JOURNAL OF HEADACHE AND PAIN
Authors: Moreno-Mayordomo, R.; Ruiz, M.; Pascual, J.; Gallego de la Sacristana, M.; Vidriales, I.; Sobrado, M.; Cernuda-Morollon, E.; Gago-Veiga, A. B.; Garcia-Azorin, D.; Telleria, J. J.; Guerrero, A. L.
Abstract
BackgroundSome 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.MethodsWe 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 43.711.8years (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.ResultsResponse 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 p id=Par4 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.
The role of calcitonin and alpha-calcitonin gene-related peptide in bone formation
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Authors: Huebner, Antje K.; Keller, Johannes; Catala-Lehnen, Philip; Perkovic, Sandra; Streichert, Thomas; Emeson, Ronald B.; Amling, Michael; Schinke, Thorsten
Abstract
The Calca gene encodes two polypeptides, calcitonin (CT) and alpha-calcitonin gene-related peptide (alpha-CGRP), generated through alternative splicing. While CT, a hormone mainly produced by thyroidal C cells, has been described as a major regulator of bone resorption, alpha-CGRP, a neuropeptide expressed in the cells of the central and peripheral nervous system, is mostly known as a regulator of vascular tone. Surprisingly, the generation and skeletal analyses of two mouse deficiency models has recently uncovered a physiological function for both peptides in the regulation of bone formation. In the first model, where the replacement of exons 2-5 of the Calca gene resulted in the combined deficiency of CT and alpha-CGRP, an increased bone formation rate (BFR) was observed, whereas decreased BFR was found in the second model, where the introduction of a translational termination codon into exon 5 of the Calca gene resulted in the specific absence of alpha-CGRP. (C) 2008 Elsevier Inc. All rights reserved.