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Abstract
Background
Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies have emerged as promising therapeutic options for the treatment of chronic migraine. However, treatment response varies considerably among individuals, suggesting a potential role for genetic factors. This study aimed to identify genetic variants affecting the efficacy of anti-CGRP monoclonal antibody therapy in chronic migraine among the Han Chinese population in Taiwan to enhance treatment precision and to understand the genetic architecture of migraine.
Methods
We conducted a quantitative trait locus (QTL) association study in patients with chronic migraines from a tertiary medical center in Taiwan using the Taiwan Precision Medicine Array Chip. The patients received fremanezumab or galcanezumab for at least 12 weeks. Treatment efficacy was assessed based on the improvement rate in monthly migraine days. Genetic variants were identified, and their associations with treatment efficacy were examined through quantitative trait loci analysis, linkage disequilibrium studies, and functional annotations using the Gene Ontology database.
Results
Six single nucleotide polymorphisms (SNPs) relative variants were significantly associated with anti-CGRP therapy response (p < 1 × 10− 7): rs116870564, rs75244870, rs56216870, rs12938101, rs74655790, and rs149540851. These variants are located in or near genes, including LRRC4C, ATAD2B, and OXR1, which are involved in neuronal development, DNA-dependent ATPase activity, and oxidation-reduction processes, respectively. The rs116870564 variant in LRRC4C showed the strongest association (β = -0.551, p = 6.65 × 10− 9). The functional impact of these variants is attributed to their regulatory effects on gene expression, which are influenced by intron splicing regulation, transcription factors, and changes in chromatin structure.
Conclusion
The identification of key genetic markers associated with response to anti-CGRP therapy emphasizes the importance of genetic variability in treatment efficacy. This could lead to more personalized chronic migraine management strategies and tailored therapeutic approaches based on individual genetic profiles. Further research in larger, diverse populations is warranted to validate these findings and refine our understanding of the role of CGRP in chronic migraine pathophysiology.
Trial registration
Not applicable.
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Details
1 National Defense Medical Center, School of Medicine, Taipei, Taiwan (GRID:grid.260565.2) (ISNI:0000 0004 0634 0356); National Defense Medical Center, Department of Emergency, Tri-Service General Hospital, Taipei, Taiwan (GRID:grid.260565.2) (ISNI:0000 0004 0634 0356)
2 National Defense Medical Center, Center for Precision Medicine and Genomics, Tri-Service General Hospital, Taipei, Taiwan (GRID:grid.260565.2) (ISNI:0000 0004 0634 0356)
3 National Defense Medical Center, School of Medicine, Taipei, Taiwan (GRID:grid.260565.2) (ISNI:0000 0004 0634 0356); National Defense Medical Center, Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, Taipei, Taiwan (GRID:grid.260565.2) (ISNI:0000 0004 0634 0356)
4 National Defense Medical Center, School of Medicine, Taipei, Taiwan (GRID:grid.260565.2) (ISNI:0000 0004 0634 0356); Tri-Service General Hospital, National Defense Medical Center, Department of Neurology, Taipei, Taiwan (GRID:grid.278244.f) (ISNI:0000 0004 0638 9360)
5 National Defense Medical Center, School of Medicine, Taipei, Taiwan (GRID:grid.260565.2) (ISNI:0000 0004 0634 0356); National Defense Medical Center, Department of Neurology, Songshan Branch, Tri-Service General Hospital, Taipei, Taiwan (GRID:grid.260565.2) (ISNI:0000 0004 0634 0356)