Variability in oxidative stress-related genes (SOD2, CAT, GPX1, GSTP1, NOS3, NFE2L2, and UCP2) and susceptibility to migraine clinical phenotypes and features

Abstract

IntroductionMigraine is a complex disorder with genetic and environmental inputs. Cumulative evidence implicates oxidative stress (OS) in migraine pathophysiology while genetic variability may influence an individuals' oxidative/antioxidant capacity. Aim of the current study was to investigate the impact of eight common OS-related genetic variants [rs4880 (SOD2), rs1001179 (CAT), rs1050450 (GPX1), rs1695 (GSTP1), rs1138272 (GSTP1), rs1799983 (NOS3), rs6721961 (NFE2L2), rs660339 (UCP2)] in migraine susceptibility and clinical features in a South-eastern European Caucasian population.MethodsGenomic DNA samples from 221 unrelated migraineurs and 265 headache-free controls were genotyped for the selected genetic variants using real-time PCR (melting curve analysis).ResultsAlthough allelic and genotypic frequency distribution analysis did not support an association between migraine susceptibility and the examined variants in the overall population, subgroup analysis indicated significant correlation between NOS3 rs1799983 and migraine susceptibility in males. Furthermore, significant associations of CAT rs1001179 and GPX1 rs1050450 with disease age-at-onset and migraine attack duration, respectively, were revealed. Lastly, variability in the CAT, GSTP1 and UCP2 genes were associated with sleep/weather changes, alcohol consumption and physical exercise, respectively, as migraine triggers.DiscussionHence, the current findings possibly indicate an association of OS-related genetic variants with migraine susceptibility and clinical features, further supporting the involvement of OS and genetic susceptibility in migraine.

Association of Oxidative-Stress-Related Gene Polymorphisms with Pain-Related Temporomandibular Disorders and Oral Behavioural Habits

“…Papasavva et al investigated how variabilities in SNPs, including rs4880, rs1001179, and rs1050450, are related to susceptibility to the clinical phenotypes and features of migraine. What they found is that homozygosity for the minor T allele (rs1001179) was associated with the later age at the onset when compared to homozygosity for the more common allele C [ 45 ]. It would be interesting to further investigate the connection between TMD and migraine onset and depression.…”

“…It would be interesting to further investigate the connection between TMD and migraine onset and depression. Considering SOD2 , no significant association was found for rs4880 variants for clinical features of migraine [ 45 ]. One case–control study reported that there was a lack of association between the SNPs of oxidative-stress-related genes (among which was rs4880 of SOD2 ) and chronic migraine [ 46 ].…”

“…The minor T allele has been linked to lower GPX1 activity [ 49 ]. This polymorphism has been linked to a number of diseases, including peripheral neuropathy, cardiovascular illness, and migraine [ 45 , 50 , 51 ]. The genotype containing two copies of the T allele was associated with patients who experienced longer migraine episodes than patients who had shorter migraine attacks, indicating that the presence of the T allele appears to be connected to longer migraine attacks [ 45 ].…”

“…This polymorphism has been linked to a number of diseases, including peripheral neuropathy, cardiovascular illness, and migraine [ 45 , 50 , 51 ]. The genotype containing two copies of the T allele was associated with patients who experienced longer migraine episodes than patients who had shorter migraine attacks, indicating that the presence of the T allele appears to be connected to longer migraine attacks [ 45 ]. We found that the individuals carrying genotype TT of rs1050450 are at a higher risk for experiencing high-frequency waking-state parafunction.…”

Genetic Variability in Vitamin D Receptor and Migraine Susceptibility: A Southeastern European Case-Control Study

“…Although the pathophysiology of the disease has not been fully elucidated, among the proposed mechanisms being implicated are the activation of the trigeminovascular system, cortical spreading depression, inflammation and vascular dysfunction [ 3 ]. Besides environmental factors, migraine is largely affected by genetic factors, with several genetic variants, each having a minor effect contributing to its liability [ 4 , 5 , 6 ].…”