School of Medicine, National Defense Medical Center, Taipei, Taiwan.
Department of Emergency, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
J Headache Pain. 2024 Sep 12;25(1):149. doi: 10.1186/s10194-024-01850-y.
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.
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.
Six single nucleotide polymorphisms (SNPs) relative variants were significantly associated with anti-CGRP therapy response (p < 1 × 10): 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). 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.
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.
Not applicable.
抗降钙素基因相关肽（CGRP）单克隆抗体已成为治疗慢性偏头痛的有前途的治疗选择。然而，个体之间的治疗反应差异很大，表明遗传因素可能起作用。本研究旨在鉴定影响台湾汉族人群慢性偏头痛中抗 CGRP 单克隆抗体治疗疗效的遗传变异，以提高治疗精度并了解偏头痛的遗传结构。
我们使用台湾精准医学阵列芯片对来自台湾一家三级医疗中心的慢性偏头痛患者进行了数量性状基因座（QTL）关联研究。患者接受了弗雷美昔单抗或加奈昔单抗治疗至少 12 周。根据每月偏头痛天数的改善率评估治疗效果。通过定量性状基因座分析、连锁不平衡研究和使用基因本体数据库进行的功能注释来鉴定遗传变异，并检查其与治疗效果的关联。
与抗 CGRP 治疗反应显著相关的六个单核苷酸多态性（SNP）相对变体（p < 1×10）：rs116870564、rs75244870、rs56216870、rs12938101、rs74655790 和 rs149540851。这些变体位于或靠近基因，包括 LRRC4C、ATAD2B 和 OXR1，它们分别参与神经元发育、DNA 依赖性 ATP 酶活性和氧化还原过程。LRRC4C 中的 rs116870564 变体与最强关联（β=-0.551，p=6.65×10）。这些变体的功能影响归因于它们对基因表达的调节作用，这受到内含子剪接调节、转录因子和染色质结构变化的影响。
与抗 CGRP 治疗反应相关的关键遗传标记的鉴定强调了遗传变异性在治疗效果中的重要性。这可能导致根据个体遗传谱制定更个性化的慢性偏头痛管理策略和定制的治疗方法。需要在更大、更多样化的人群中进行进一步研究，以验证这些发现并完善我们对 CGRP 在慢性偏头痛病理生理学中的作用的理解。
不适用。
