Exploring the Association of Migraine Susceptibility SNPs With the Risk of Chronic Migraine

IF 3.4 2区医学 Q1 ANESTHESIOLOGY

European Journal of Pain Pub Date : 2025-09-05 DOI:10.1002/ejp.70120

Sarah Cargnin, Martina Giacon, Elisa Del Corona, Anna Maria Zanaboni, Sara Facchetti, Roberto De Icco, Gloria Vaghi, Grazia Sances, Natascia Ghiotto, Elena Guaschino, Daniele Martinelli, Rosaria Greco, Cristina Tassorelli, Salvatore Terrazzino, Marta Allena

{"title":"Exploring the Association of Migraine Susceptibility SNPs With the Risk of Chronic Migraine","authors":"Sarah Cargnin, Martina Giacon, Elisa Del Corona, Anna Maria Zanaboni, Sara Facchetti, Roberto De Icco, Gloria Vaghi, Grazia Sances, Natascia Ghiotto, Elena Guaschino, Daniele Martinelli, Rosaria Greco, Cristina Tassorelli, Salvatore Terrazzino, Marta Allena","doi":"10.1002/ejp.70120","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Although robust genetic markers for episodic migraine (EM) have been identified, variants associated with chronic migraine (CM) are still unknown. Given the potential pathophysiologic overlap between EM and CM, we investigated whether six single nucleotide polymorphisms (SNPs), robustly associated with EM susceptibility (<i>LRP1</i> rs11172113, <i>PRDM16</i> rs10797381, <i>FHL5</i> rs7775721, <i>TRPM8</i> rs10166942, near <i>TSPAN2</i> rs2078371 and <i>MEF2D</i> rs1925950) also play a role in the risk of developing CM.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>A total of 200 EM and 202 CM participants were prospectively included. Genotyping of selected SNPs was performed by TaqMan real-time PCR in 192 individuals with EM and 198 with CM who consented to genetic analysis. A validation group of 312 healthy individuals was used. Genetic associations were assessed by logistic regression using dominant, recessive, and allelic models.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>In multivariable logistic regression analysis, <i>LRP1</i> rs11172113 T>C and (near) <i>TSPAN2</i> rs2078371 T>C were nominally associated with CM. However, only the association for <i>LRP1</i> rs11172113 survived Bonferroni correction, with carriers of the minor C allele (genotypes T/C or C/C) having a lower risk of CM compared to wild-type homozygous subjects (OR: 0.38; 95% CI: 0.20–0.71; <i>p</i>-value: 0.0025). This protective effect was also observed in the analysis comparing CM participants with healthy controls.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Carriers of the minor allele of <i>LRP1</i> rs11172113 have a reduced risk of CM. However, further large-scale studies, ideally with a multicentre design, are warranted to confirm the association between <i>LRP1</i> rs11172113 and CM.</p>\n </section>\n \n <section>\n \n <h3> Significance Statement</h3>\n \n <p>This study identified an association between the minor allele of <i>LRP1</i> rs11172113 (low-density lipoprotein receptor-related protein 1, a receptor with key roles in lipid metabolism, vascular integrity, and inflammation control) and a reduced risk of chronic migraine. These findings support the hypothesis that episodic and chronic migraine share genetic risk factors and suggest a potential protective role for this variant.</p>\n </section>\n </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"29 9","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Pain","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ejp.70120","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANESTHESIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Although robust genetic markers for episodic migraine (EM) have been identified, variants associated with chronic migraine (CM) are still unknown. Given the potential pathophysiologic overlap between EM and CM, we investigated whether six single nucleotide polymorphisms (SNPs), robustly associated with EM susceptibility (LRP1 rs11172113, PRDM16 rs10797381, FHL5 rs7775721, TRPM8 rs10166942, near TSPAN2 rs2078371 and MEF2D rs1925950) also play a role in the risk of developing CM.

Methods

A total of 200 EM and 202 CM participants were prospectively included. Genotyping of selected SNPs was performed by TaqMan real-time PCR in 192 individuals with EM and 198 with CM who consented to genetic analysis. A validation group of 312 healthy individuals was used. Genetic associations were assessed by logistic regression using dominant, recessive, and allelic models.

Results

In multivariable logistic regression analysis, LRP1 rs11172113 T>C and (near) TSPAN2 rs2078371 T>C were nominally associated with CM. However, only the association for LRP1 rs11172113 survived Bonferroni correction, with carriers of the minor C allele (genotypes T/C or C/C) having a lower risk of CM compared to wild-type homozygous subjects (OR: 0.38; 95% CI: 0.20–0.71; p-value: 0.0025). This protective effect was also observed in the analysis comparing CM participants with healthy controls.

Conclusion

Carriers of the minor allele of LRP1 rs11172113 have a reduced risk of CM. However, further large-scale studies, ideally with a multicentre design, are warranted to confirm the association between LRP1 rs11172113 and CM.

Significance Statement

This study identified an association between the minor allele of LRP1 rs11172113 (low-density lipoprotein receptor-related protein 1, a receptor with key roles in lipid metabolism, vascular integrity, and inflammation control) and a reduced risk of chronic migraine. These findings support the hypothesis that episodic and chronic migraine share genetic risk factors and suggest a potential protective role for this variant.

查看原文本刊更多论文

探讨偏头痛易感性snp与慢性偏头痛风险的关系

背景虽然已经确定了发作性偏头痛（EM）的强大遗传标记，但与慢性偏头痛（CM）相关的变异仍然未知。鉴于EM和CM之间潜在的病理生理重叠，我们研究了与EM易感性密切相关的6个单核苷酸多态性（LRP1 rs11172113、PRDM16 rs10797381、FHL5 rs7775721、TRPM8 rs10166942、TSPAN2 rs2078371和MEF2D rs1925950）是否也在CM发生风险中发挥作用。方法前瞻性纳入200名EM参与者和202名CM参与者。对192例EM患者和198例CM患者同意进行遗传分析，采用TaqMan实时PCR对选定的snp进行基因分型。采用312名健康个体作为验证组。遗传关联通过使用显性、隐性和等位基因模型的逻辑回归进行评估。结果在多变量logistic回归分析中，LRP1 rs11172113 T>；C和（近）TSPAN2 rs2078371 T>；C名义上与CM相关。然而，只有与LRP1 rs11172113相关的基因在Bonferroni校正中存活下来，与野生型纯合子受试者相比，携带少量C等位基因（基因型T/C或C/C）的受试者患CM的风险较低（or: 0.38; 95% CI: 0.20-0.71； p值：0.0025）。在比较CM参与者与健康对照者的分析中也观察到这种保护作用。结论携带LRP1次要等位基因rs11172113的人群患CM的风险较低。然而，进一步的大规模研究，最好是多中心设计，有必要确认LRP1 rs11172113与CM之间的关联。本研究确定了LRP1 rs11172113（低密度脂蛋白受体相关蛋白1，一种在脂质代谢、血管完整性和炎症控制中起关键作用的受体）的次要等位基因与慢性偏头痛风险降低之间的关联。这些发现支持了发作性偏头痛和慢性偏头痛具有相同遗传风险因素的假设，并表明这种变异具有潜在的保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

European Journal of Pain 医学-临床神经学

CiteScore

7.50

自引率

5.60%

发文量

163

审稿时长

4-8 weeks

期刊介绍： European Journal of Pain (EJP) publishes clinical and basic science research papers relevant to all aspects of pain and its management, including specialties such as anaesthesia, dentistry, neurology and neurosurgery, orthopaedics, palliative care, pharmacology, physiology, psychiatry, psychology and rehabilitation; socio-economic aspects of pain are also covered. Regular sections in the journal are as follows: • Editorials and Commentaries • Position Papers and Guidelines • Reviews • Original Articles • Letters • Bookshelf The journal particularly welcomes clinical trials, which are published on an occasional basis. Research articles are published under the following subject headings: • Neurobiology • Neurology • Experimental Pharmacology • Clinical Pharmacology • Psychology • Behavioural Therapy • Epidemiology • Cancer Pain • Acute Pain • Clinical Trials.