TRPM8 genetic variant is associated with chronic migraine and allodynia

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Many 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.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>The associations of six SNPs identified from our previous study, including <jats:italic>TRPM8</jats:italic> rs10166942, <jats:italic>LRP1</jats:italic> rs1172113, <jats:italic>DLG2</jats:italic> rs655484, <jats:italic>GFRA1</jats:italic> rs3781545, <jats:italic>UPP2</jats:italic> rs7565931, and <jats:italic>GPR39</jats:italic> 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.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>In 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, <jats:italic>TRPM8</jats:italic> 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%, <jats:italic>p</jats:italic> = 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, <jats:italic>p</jats:italic> < 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.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p><jats:italic>TRPM8</jats:italic> 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.</jats:p> </jats:sec>