University of Kentucky
The Effects of TRPM8 Gene Variants on Migraine
Institution
University of Kentucky
Faculty Advisor/ Mentor
Steven Estus
Abstract
TRPM8 is a member of the transient receptor potential cation channel family. TRPM8 is a ligand-gated ion channel protein that is activated by cold or menthol. When activated, the TRPM8 protein lets Na+ and Ca2+ ions enter the cell, which generate depolarization and action potentials. The somatosensory cortex in the brain perceives the incoming signal as the sensation of cold pain. Markus Schurks’ research found that heredity is an important aspect in susceptibility to migraines. About 50% of effected individuals have a first-degree relative who suffers from migraine which supports the idea that migraine risk is modulated by polymorphisms in the human genome [4]. A single nucleotide polymorphism (SNP), rs10166942, was recently found to be related to migraine risk in three large genome-wide association studies [1-3]. The minor allele of the SNP has reduced risk of migraines. More recently, the minor SNP allele was also associated with less intense cold pain. Two SNPs, rs13004520 and rs17868387, were found that are co-inherited with one another 100% and 33% of the time with the migraine SNP. Both of these SNPs change TRPM8 amino acids (missense mutations). These mutations are predicted by poly-Phen to alter TRPM8 function. The minor and major alleles of the TRPM8 gene are being cloned and transfected into HEK293 cells. Using menthol or cold stimulus, the response of the two forms of the TRPM8 cells will be tested. When stimulated by cold or menthol, the minor allele of the two forms should have less Na+ and Ca2+ ions in the cells. This is because people with the minor allele reported less intense cold pain. Elucidating the function of these two SNPs will thus show how we may be able to alter TRPM8 function to reduce the risk of migraine.
The Effects of TRPM8 Gene Variants on Migraine
TRPM8 is a member of the transient receptor potential cation channel family. TRPM8 is a ligand-gated ion channel protein that is activated by cold or menthol. When activated, the TRPM8 protein lets Na+ and Ca2+ ions enter the cell, which generate depolarization and action potentials. The somatosensory cortex in the brain perceives the incoming signal as the sensation of cold pain. Markus Schurks’ research found that heredity is an important aspect in susceptibility to migraines. About 50% of effected individuals have a first-degree relative who suffers from migraine which supports the idea that migraine risk is modulated by polymorphisms in the human genome [4]. A single nucleotide polymorphism (SNP), rs10166942, was recently found to be related to migraine risk in three large genome-wide association studies [1-3]. The minor allele of the SNP has reduced risk of migraines. More recently, the minor SNP allele was also associated with less intense cold pain. Two SNPs, rs13004520 and rs17868387, were found that are co-inherited with one another 100% and 33% of the time with the migraine SNP. Both of these SNPs change TRPM8 amino acids (missense mutations). These mutations are predicted by poly-Phen to alter TRPM8 function. The minor and major alleles of the TRPM8 gene are being cloned and transfected into HEK293 cells. Using menthol or cold stimulus, the response of the two forms of the TRPM8 cells will be tested. When stimulated by cold or menthol, the minor allele of the two forms should have less Na+ and Ca2+ ions in the cells. This is because people with the minor allele reported less intense cold pain. Elucidating the function of these two SNPs will thus show how we may be able to alter TRPM8 function to reduce the risk of migraine.