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1000 Titel
  • Role of CGRP pathway polymorphisms in migraine: a systematic review and impact on CGRP mAbs migraine therapy
1000 Autor/in
  1. Scuteri, Damiana |
  2. Corasaniti, Maria Tiziana |
  3. Tonin, Paolo |
  4. Nicotera, Pierluigi |
  5. Bagetta, Giacinto |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-07-30
1000 Erschienen in
1000 Quellenangabe
  • 22(1):87
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1186/s10194-021-01295-7 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325208/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • 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.
1000 Sacherschließung
lokal SNPs
lokal RAMP 1
lokal methylation
lokal Humans [MeSH]
lokal CLR
lokal Migraine Disorders/genetics [MeSH]
lokal CALCRL
lokal Antibodies, Monoclonal [MeSH]
lokal RCP
lokal CGRP
lokal Translational Research in Headache
lokal CALC A
lokal AMYLIN-1
lokal polymorphisms
lokal systematic review
lokal Calcitonin [MeSH]
lokal Calcitonin Gene-Related Peptide Receptor Antagonists [MeSH]
lokal migraine
lokal epigenetic
lokal Calcitonin Gene-Related Peptide [MeSH]
lokal Research Article
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