• Yu-Hsiang Ling, Shih-Pin Chen, Cathy Shen-Jang Fann, Shuu-Jiun Wang, and Yen-Feng Wang.
• Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
• J Headache Pain. 2019 Dec 16; 20 (1): 115.

BackgroundMany single nucleotide polymorphisms (SNPs) have been reported to be associated with migraine susceptibility. However, evidences for their associations with migraine endophenotypes or subtypes are scarce. We aimed to investigate the associations of pre-identified migraine susceptibility loci in Taiwanese with migraine endophenotypes or subtypes, including chronic migraine and allodynia.MethodsThe associations of six SNPs identified from our previous study, including TRPM8 rs10166942, LRP1 rs1172113, DLG2 rs655484, GFRA1 rs3781545, UPP2 rs7565931, and GPR39 rs10803531, and migraine endophenotypes, including chronic migraine and allodynia were tested. Significant associations in the discovery cohort were validated in the replication cohort. The adjusted odds ratios (aOR) were calculated after controlling for confounders.ResultsIn total, 1904 patients (mean age 37.5 ± 12.2 years old, female ratio: 77.7%) including 1077 in the discovery cohort and 827 in the replication cohort were recruited. Of them, 584 (30.7%) had chronic migraine. Of the 6 investigated SNPs, TRPM8 rs10166942 T allele-carrying patients were more likely to have chronic migraine than non-T allele carriers in both discovery and replication cohorts and combined samples (33.7% vs. 25.8%, p = 0.004, aOR = 1.62). In addition, T allele carriers reported more allodynic symptoms than non-T allele carriers (3.5 ± 3.7 vs. 2.6 ± 2.8, p < 0.001). However, allodynia severity did not differ between episodic and chronic migraine patients. No further correlations between genetic variants and endophenotypes were noted for the other SNPs.ConclusionsTRPM8 may contribute to the pathogenesis of chronic migraine. However, our study did not support allodynia as a link between them. The underlying mechanisms deserve further investigations.

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