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Role of CGRP pathway polymorphisms in migraine: a systematic review and impact on CGRP mAbs migraine therapy

BACKGROUND: the interest of clinical reaseach in polymorphisms and epigenetics in migraine has been growing over the years. Due to the new era of preventative migraine treatment opened by monoclonal antibodies (mAbs) targeting the signaling of the calcitonin-gene related peptide (CGRP), the present...

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Autores principales: Scuteri, Damiana, Corasaniti, Maria Tiziana, Tonin, Paolo, Nicotera, Pierluigi, Bagetta, Giacinto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Milan 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325208/
https://www.ncbi.nlm.nih.gov/pubmed/34330208
http://dx.doi.org/10.1186/s10194-021-01295-7
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author Scuteri, Damiana
Corasaniti, Maria Tiziana
Tonin, Paolo
Nicotera, Pierluigi
Bagetta, Giacinto
author_facet Scuteri, Damiana
Corasaniti, Maria Tiziana
Tonin, Paolo
Nicotera, Pierluigi
Bagetta, Giacinto
author_sort Scuteri, Damiana
collection PubMed
description BACKGROUND: the interest of clinical reaseach in polymorphisms and epigenetics in migraine has been growing over the years. Due to the new era of preventative migraine treatment opened by monoclonal antibodies (mAbs) targeting the signaling of the calcitonin-gene related peptide (CGRP), the present systematic review aims at identifying genetic variants occurring along the CGRP pathway and at verifying whether these can affect the clinical features and the course of disease and the responsiveness of patients to therapy. METHODS: the literature search has been conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science, the Human Genome Epidemiology (HuGE) Published Literature database (Public Health Genomics Knowledge Base) and Clinicaltrials.gov from database inception until April 1, 2021. The process of identification and selection of the studies included in the analysis has followed the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) criteria for systematic reviews and meta-analyses and the guidance from the Human Genome Epidemiology Network for reporting gene-disease associations. RESULTS: the search has retrieved 800 results, among which only 7 studies have met the eligibility criteria for inclusion in the analysis. The latter are case-control studies of genetic association and an exploratory analysis and two polymorphisms have been detected as the most recurring: the rs3781719 (T > C) of the CALC A gene encoding CGRP and the rs7590387 of the gene encoding the receptor activity-modifying protein (RAMP) 1 (C > G). Only one study assessing the methylation pattern with regard to CGRP pathway has been found from the search. No genetic association studies investigating the possible effect of genetic variants affecting CGRP signaling on the responsiveness to the most recent pharmacological approaches, i.e. anti-CGRP(R) mAbs, gepants and ditans, have been published. According to the Human Genome Epidemiology (HuGE) systematic reviews and meta-analyses risk-of-bias score for genetic association studies, the heterogeneity between and across studies and the small sample size do not allow to draw conclusions and prompt future studies. CONCLUSIONS: adequately powered, good quality genetic association studies are needed to understand the impact of genetic variants affecting the pathway of CGRP on migraine susceptibility and clinical manifestation and to predict the response to therapy in terms of efficacy and safety.
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spelling pubmed-83252082021-08-02 Role of CGRP pathway polymorphisms in migraine: a systematic review and impact on CGRP mAbs migraine therapy Scuteri, Damiana Corasaniti, Maria Tiziana Tonin, Paolo Nicotera, Pierluigi Bagetta, Giacinto J Headache Pain Research Article BACKGROUND: the interest of clinical reaseach in polymorphisms and epigenetics in migraine has been growing over the years. Due to the new era of preventative migraine treatment opened by monoclonal antibodies (mAbs) targeting the signaling of the calcitonin-gene related peptide (CGRP), the present systematic review aims at identifying genetic variants occurring along the CGRP pathway and at verifying whether these can affect the clinical features and the course of disease and the responsiveness of patients to therapy. METHODS: the literature search has been conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science, the Human Genome Epidemiology (HuGE) Published Literature database (Public Health Genomics Knowledge Base) and Clinicaltrials.gov from database inception until April 1, 2021. The process of identification and selection of the studies included in the analysis has followed the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) criteria for systematic reviews and meta-analyses and the guidance from the Human Genome Epidemiology Network for reporting gene-disease associations. RESULTS: the search has retrieved 800 results, among which only 7 studies have met the eligibility criteria for inclusion in the analysis. The latter are case-control studies of genetic association and an exploratory analysis and two polymorphisms have been detected as the most recurring: the rs3781719 (T > C) of the CALC A gene encoding CGRP and the rs7590387 of the gene encoding the receptor activity-modifying protein (RAMP) 1 (C > G). Only one study assessing the methylation pattern with regard to CGRP pathway has been found from the search. No genetic association studies investigating the possible effect of genetic variants affecting CGRP signaling on the responsiveness to the most recent pharmacological approaches, i.e. anti-CGRP(R) mAbs, gepants and ditans, have been published. According to the Human Genome Epidemiology (HuGE) systematic reviews and meta-analyses risk-of-bias score for genetic association studies, the heterogeneity between and across studies and the small sample size do not allow to draw conclusions and prompt future studies. CONCLUSIONS: adequately powered, good quality genetic association studies are needed to understand the impact of genetic variants affecting the pathway of CGRP on migraine susceptibility and clinical manifestation and to predict the response to therapy in terms of efficacy and safety. Springer Milan 2021-07-30 /pmc/articles/PMC8325208/ /pubmed/34330208 http://dx.doi.org/10.1186/s10194-021-01295-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Scuteri, Damiana
Corasaniti, Maria Tiziana
Tonin, Paolo
Nicotera, Pierluigi
Bagetta, Giacinto
Role of CGRP pathway polymorphisms in migraine: a systematic review and impact on CGRP mAbs migraine therapy
title Role of CGRP pathway polymorphisms in migraine: a systematic review and impact on CGRP mAbs migraine therapy
title_full Role of CGRP pathway polymorphisms in migraine: a systematic review and impact on CGRP mAbs migraine therapy
title_fullStr Role of CGRP pathway polymorphisms in migraine: a systematic review and impact on CGRP mAbs migraine therapy
title_full_unstemmed Role of CGRP pathway polymorphisms in migraine: a systematic review and impact on CGRP mAbs migraine therapy
title_short Role of CGRP pathway polymorphisms in migraine: a systematic review and impact on CGRP mAbs migraine therapy
title_sort role of cgrp pathway polymorphisms in migraine: a systematic review and impact on cgrp mabs migraine therapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325208/
https://www.ncbi.nlm.nih.gov/pubmed/34330208
http://dx.doi.org/10.1186/s10194-021-01295-7
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